UI - 11584558
AU - Dorval M; Maunsell E; Dugas MJ; Simard J
Support groups for people carrying a BRCA mutation.
SO - CMAJ 2001 Sep 18;165(6):740; discussion 740, 742
UI - 11877310
AU - Tobin G; Thunberg U; Johnson A; Thorn I; Soderberg O; Hultdin M; Botling
J; Enblad G; Sallstrom J; Sundstrom C; Roos G; Rosenquist R
Somatically mutated Ig V(H)3-21 genes characterize a new subset of
chronic lymphocytic leukemia.
SO - Blood 2002 Mar 15;99(6):2262-4
AD - Department of Genetics and Pathology, Uppsala University, SE-751 85
Recent studies on the immunoglobulin variable heavy chain (IgV(H)) genes
have revealed that B-cell chronic lymphocytic leukemia (B-CLL) consists
of at least 2 clinical entities with either somatically mutated or
unmutated V(H) genes. We have analyzed the V(H) gene mutation status and
V(H) gene usage in 119 B-CLL cases and correlated them to overall
survival. A novel finding was the preferential use of the V(H)3-21 gene
in mutated cases, whereas biased V(H)1-69 gene usage was found in
unmutated cases as previously reported. Interestingly, the subset of
mutated cases using the V(H)3-21 gene displayed distinctive
genotypic/phenotypic characteristics with shorter average length of the
complementarity determining region 3 and clonal expression of lambda
light chains. In addition, this mutated subset showed significantly
shorter survival than other mutated cases and a similar clinical course
to unmutated cases. We therefore suggest that B-CLL cases with mutated
V(H)3-21 genes may constitute an additional entity of B-CLL.
UI - 11954751
AU - Ohya K; Abo W; Tamaki H; Sugawara C; Endo T; Nomachi S; Fukushi M;
Kinebuchi M; Matsuura A
Presymptomatic diagnosis of Wilson disease associated with a novel
mutation of the ATP7B gene.
SO - Eur J Pediatr 2002 Feb;161(2):124-6
UI - 12203775
AU - Azarschab P; Porschen R; Gregor M; Blin N; Holzmann K
Epigenetic control of the E-cadherin gene (CDH1) by CpG methylation in
colectomy samples of patients with ulcerative colitis.
SO - Genes Chromosomes Cancer 2002 Oct;35(2):121-6
AD - Division of Molecular Genetics, Institute of Anthropology and Human
Genetics, University of Tubingen, Tubingen, Germany. firstname.lastname@example.org
E-cadherin belongs to the cadherin family of calcium-dependent
cell-adhesion molecules. The cadherins play an essential role in
biological processes such as ordering of cell sorting, migration, and
differentiation, and their malfunctioning is connected with neoplasia.
Neoplastic progression in patients with chronic ulcerative colitis is
characterized by the development of epithelial dysplasia.
Transcriptional silencing of tumor-suppressor genes by promoter
methylation has been observed in different types of human cancers and
dysplasia. To explore the mode of E-cadherin regulation, 156 biopsy
samples from 26 patients with long-standing ulcerative colitis were
screened. To detect the methylation status of our samples, a
methylation-specific PCR was applied. Methylation of the E-cadherin
(CDH1) promoter was detected in 93% of the patients with dysplastic
biopsy samples, in contrast to only 6% of the patients without dysplasia
(P < 0.001). We also examined the level of synthesis of E-cadherin
protein by immunohistochemical staining in different paraffin-embedded
samples of dysplastic and non-dysplastic origin in a subset of our
patients. Samples with dysplasia displayed reduced levels, whereas
samples without dysplasia revealed normal E-cadherin protein synthesis.
These results show that the E-cadherin promoter is subjected to
epigenetic control in colorectal ulceration. Obviously, this event may
play an important role in the progression from chronic inflammation to
colorectal cancer. For this reason, methylation of the CDH1 promoter is
an attractive new biomarker for detecting ulcerative colitis patients
with a high risk for developing colorectal cancers. Copyright 2002
UI - 12203777
AU - Chen YJ; Chen PJ; Lee MC; Yeh SH; Hsu MT; Lin CH
Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by
comparative genomic hybridization.
SO - Genes Chromosomes Cancer 2002 Oct;35(2):138-43
AD - Center for General Education, National Yang-Ming University, Taipei,
Hepatic adenoma (HA) and focal nodular hyperplasia (FNH) are two common
non-malignant tumors of the liver. Genomic analysis on these benign
lesions may shed light on the genetic mechanism underlying liver
carcinogenesis. We used comparative genomic hybridization (CGH) to
evaluate genomic changes in eight cases of HA and six cases of FNH,
obtained by surgical procedures; the resulting chromosomal aberration
profiles were analyzed together with their pathological and clinical
manifestations. We found consistent chromosomal lesions associated with
both non-malignant hepatic tumors. The overall genomic abnormalities in
HA and FNH were much less obvious than those in hepatocellular carcinoma
(HCC). Among these limited changes, frequent gains were located on
chromosomal arms 1q (50%), 17q (50%), 1p (38%), and 11q (38%) in HA, and
on 11q (50%), 9q (33%), 17q (33%), and 22q (33%) in FNH. Gains
outnumbered losses, and HA contained more CGH abnormalities than did
FNH. Interestingly, CGH alteration hotspots found in HA, but not in FNH,
appeared largely to coincide with common genomic lesions of cancerous
HCC, suggesting an interesting relationship along the tumorigenesis
pathway of HA and HCC. Copyright 2002 Wiley-Liss, Inc.
UI - 8403599
AU - Holzgreve W; Nippert I; Ganshirt-Ahlert D; Schloo R; Miny P
Immediate and long-term applications of technology.
SO - Clin Obstet Gynecol 1993 Sep;36(3):476-84
AD - Zentrum fur Frauenheilkunde, University of Munster, FRG.
UI - 8403601
AU - Pryde PG; Drugan A; Johnson MP; Isada NB; Evans MI
Prenatal diagnosis: choices women make about pursuing testing and acting
on abnormal results.
SO - Clin Obstet Gynecol 1993 Sep;36(3):496-509
AD - Wayne State University School of Medicine, Detroit, Michigan.
UI - 7691458
AU - Elkins TE; Brown D
The cost of choice: a price too high in the triple screen for Down
SO - Clin Obstet Gynecol 1993 Sep;36(3):532-40
AD - Department of Obstetrics and Gynecology, Louisiana State University,
School of Medicine, New Orleans 70112.
UI - 7143324
AU - Rayburn WF; LaFerla JJ
Second-trimester pregnancy termination for genetic abnormalities.
SO - J Reprod Med 1982 Sep;27(9):584-8
UI - 6860595
AU - Haxton MJ; Bell J
Fetal anatomical abnormalities and other associated factors in
middle-trimester abortion and their relevance to patient counselling.
SO - Br J Obstet Gynaecol 1983 Jun;90(6):501-6
Fetuses present in 91 consecutive spontaneous or missed middle-trimester
abortions were studied anatomically and tissue karyotyping was
attempted. Anatomical abnormalities were found in 32 fetuses, two of
these also had chromosomal abnormalities, six of these abortions were
associated with other possible aetiological factors. In a further 23
pregnancies there were probably significant aetiological factors
associated with the abortion and in 10, where the fetus had arrested
growth, there were two with other possible factors. From a prospective
analysis of subsequent pregnancies it would appear that if all the
factors relating to middle-trimester abortion, including fetal autopsy,
are analysed, better patient counselling and realistic prognoses can be
given for subsequent pregnancy.
UI - 8530268
AU - Botkin JR
Fetal privacy and confidentiality.
SO - Hastings Cent Rep 1995 Sep-Oct;25(5):32-9
AD - Department of Pediatrics, University of Utah School of Medicine, USA.
UI - 9647530
AU - Yagel S; Anteby E
A rational approach to prenatal screening and intervention.
SO - Hum Reprod 1998 May;13(5):1126-8
AD - Department of Obstetrics and Gynecology, Hadssah Mt Scopus, Jerusalem,
UI - 12116225
AU - Volcik KA; Blanton SH; Kruzel MC; Townsend IT; Tyerman GH; Mier RJ;
Testing for genetic associations with the PAX gene family in a spina
SO - Am J Med Genet 2002 Jul 1;110(3):195-202
AD - Department of Pediatrics, The University of Texas Medical School at
Houston, Texas 77030, USA.
Neural tube defects (NTDs) are among the most common severely disabling
birth defects in the United States, affecting approximately 1-2 of every
1,000 live births. The etiology of NTDs is multifactorial, involving the
combined action of both genetic and environmental factors. A
nonparametric linkage method, the transmission disequilibrium test
(TDT), was utilized to determine if the genes in the PAX family play a
role in the formation of NTDs. DNA from 459 spina bifida (SB) patients
and their parents (430 mothers and 239 fathers, for a total population
of 1,128 subjects) was tested for linkage and association utilizing
polymorphic markers from within or very close to the PAX genes of
interest. Significant findings were obtained for the following markers:
marker locus D20S101 flanking the PAX1 gene (P = 0.019), marker locus
D1S228 within the PAX7 gene (P = 0.011), and marker locus D2S110 within
the PAX8 gene (P = 0.013). Even though our findings are only mildly
significant, given the known expression patterns of the PAX genes in
development and the availability of their sequences, we elected to
follow up these results by testing these genes directly for mutations
utilizing single-strand conformational analysis (SSCA) and direct
sequencing. Multiple variations were detected in each of the PAX genes
with significant TDT results; however, these variations were not passed
from parent to child in phase with the positively transmitted allele.
Therefore, it is unlikely that these variations contribute to
susceptibility for SB, but rather are previously unreported
polymorphisms. Copyright 2002 Wiley-Liss, Inc.
UI - 12353948
AU - Calvert PM; Frucht H
The genetics of colorectal cancer.
SO - Ann Intern Med 2002 Oct 1;137(7):603-12
AD - Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Colon cancer is a common disease that can be sporadic, familial, or
inherited. Recent advances have contributed to the understanding of the
molecular basis of these various patterns of colon cancer. Germline
genetic mutations are the basis of inherited colon cancer syndromes; an
accumulation of somatic mutations in a cell is the basis of sporadic
colon cancer; and, in Ashkenazi Jewish persons, a mutation that was
previously thought to be a polymorphism may cause familial colon cancer.
Mutations of three different classes of genes have been described in
colon cancer etiology: oncogenes, suppressor genes, and mismatch repair
genes. Knowledge of many of the specific mutations responsible for colon
carcinogenesis allows an understanding of the phenotypic manifestations
observed and forms the basis of genetic testing for inherited disease.
Although genetic testing is possible and available, it is only an
adjunct to the clinical management of persons at risk for colon cancer
and patients with colon cancer. As a result of advances in the
understanding of the molecular causes of colon cancer and the
availability of colon cancer screening methods such as colonoscopy, it
should be possible to prevent the vast majority of colon cancer in our
society. Practicing clinicians should recognize the patterns of clinical
colon cancer, understand its causes, and be able to use genetic testing
and endoscopic screening for prevention.
UI - 12353974
AU - Anonymous
Summaries for patients. The genetics of colorectal cancer.
SO - Ann Intern Med 2002 Oct 1;137(7):I48
UI - 12219430
AU - MacDonald DJ
Women's decisions regarding management of breast cancer risk.
SO - Medsurg Nurs 2002 Aug;11(4):183-6
AD - City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Twenty-three unaffected women with a family history of breast or ovarian
cancer participated in a study to ascertain their cancer-related
concerns, beliefs, and preferences for risk management. Their
perceptions related to breast cancer risk management options have
implications for practicing nurses.
UI - 12176179
AU - Pampanos A; Economides J; Iliadou V; Neou P; Leotsakos P; Voyiatzis N;
Eleftheriades N; Tsakanikos M; Antoniadi T; Hatzaki A; Konstantopoulou
I; Yannoukakos D; Gronskov K; Brondum-Nielsen K; Grigoriadou M;
Gyftodimou J; Iliades T; Skevas A; Petersen MB
Prevalence of GJB2 mutations in prelingual deafness in the Greek
SO - Int J Pediatr Otorhinolaryngol 2002 Sep 2;65(2):101-8
AD - Department of Genetics, Institute of Child Health, Aghia Sophia
Children's Hospital, GR-11527 Athens, Greece.
OBJECTIVE: Mutations in the gene encoding the gap junction protein
connexin 26 (GJB2) have been shown as a major contributor to prelingual,
sensorineural, nonsyndromic, recessive deafness. One specific mutation,
35delG, has accounted for the majority of the mutations detected in the
GJB2 gene in Caucasian populations. The aim of our study was to
determine the prevalence and spectrum of GJB2 mutations in prelingual
deafness in the Greek population. METHODS: In a collaboration with the
major referral centers for childhood deafness in Greece, patients were
examined by an extensive questionnaire to exclude syndromic forms and
environmental causes of deafness and by allele-specific polymerase chain
reaction (PCR) for the detection of the 35delG mutation. Patients
heterozygous for the 35delG mutation were further analyzed by direct
genomic sequencing of the coding region of the GJB2 gene. RESULTS: The
35delG mutation was found in 42.2% of the chromosomes in 45 familial
cases of prelingual, nonsyndromic deafness (18 homozygotes and 2
heterozygotes) and in 30.6% of the chromosomes in 165 sporadic cases (45
homozygotes and 11 heterozygotes). Direct genomic sequencing in
heterozygous patients revealed the L90P (2 alleles), W24X (2 alleles),
R184P (2 alleles), and 291insA (1 allele) mutations. CONCLUSION:
Mutations in the GJB2 gene are responsible for about one third of
prelingual, sensorineural, nonsyndromic deafness in the Greek
population, and allele-specific PCR is an easy screening method for the
common 35delG mutation. Copyright 2002 Elsevier Science Ireland Ltd.
UI - 11908638
AU - Liu LH; Gladwell W; Teng CT
Detection of exon polymorphisms in the human lactoferrin gene.
SO - Biochem Cell Biol 2002;80(1):17-22
AD - Gene Regulation Section, Laboratory of Reproductive and Developmental
Toxicology, National Institute of Environmental Health Sciences,
National Institutes of Health Research Triangle Park, NC 27709, USA.
We previously demonstrated that lactoferrin gene polymorphisms occur in
cancer cells of patients with leukemia and breast cancer. In this study,
we established a non-radioactive polymerase chain reaction-single strand
conformation polymorphism (PCR-SSCP) analysis, one of the most sensitive
and simplest methods to detect polymorphisms and mutations of the human
lactoferrin gene. We optimized the PCR conditions for nine different DNA
templates and 16 pairs of exon primers for SSCP analysis. The DNA
templates used in the analyses were prepared from a cosmid clone (CT6-1)
that contains the human lactoferrin gene, human placental tissue,
leukocytes from 10 normal volunteers, leukemic cells of two patients,
and previously established three breast and two leukemic cell lines.
With the appropriate exon-primer sets, PCR products from exon I to exon
16 of the lactoferrin gene were generated from the DNA templates and
analyzed by SSCP. Compared with the homogenous cloned DNA, lactoferrin
gene polymorphisms were detected within exons 2, 5, 7, 9, 13, 14, and 15
of the normal placental and leukocyte DNA. In addition, abnormal
migration patterns of the lactoferrin gene in cancer cells were detected
in exons 4, 5, 13, 14, and 15. The PCR-SSCP band migration patterns can
be attributed either to gene polymorphism in normal cells or to DNA
mutations in cancer cells and the employed method cannot distinguish
between them. Nonetheless, the present analysis suggests that genetic
polymorphisms of the lactoferrin gene exist in selected exons and
additional mutations of the lactoferrin gene do occur in the cancer
UI - 12242882
AU - Otlowski MF; Taylor SD; Barlow-Stewart KK
Major study commencing into genetic discrimination in Australia.
SO - J Law Med 2002 Aug;10(1):41-8
AD - Faculty of Law, University of Tasmania, GPO Box 252-89, Hobart, Tas,
This article describes a nationwide empirical study that will be
undertaken during the next three years into the newly emerging
phenomenon of genetic discrimination. In particular, the study aims to
investigate the nature and extent of genetic discrimination in Australia
across three key perspectives: consumers, third parties and the legal
system. Further, the study aims to examine the social and legal
implications of genetic discrimination, with a view to making
recommendations for use in the Australian legal and policy context. It
is anticipated that the data produced from this multifaceted
investigation will assist in identifying areas where legal or other
reforms are required. It will contribute significant baseline data for
facilitating ongoing assessment of the nature and extent of the problem,
as well as for longitudinal evaluation of the impact and effectiveness
of any reforms which may be introduced in the future to address the
UI - 10639883
AU - Reynolds PP; Benkendorf JL
Genes and generalists: why we need professionals with added
SO - West J Med 1999 Nov-Dec;171(5-6):375-9
AD - Department of Medicine and History, Johns Hopkins University School of
Medicine, Baltimore, MD, USA. email@example.com
UI - 11954859
AU - Tedde A; Nacmias B; Cellini E; Bagnoli S; Sorbi S
Lack of association between NOS3 poly morphism and Italian sporadic and
familial Alzheimer's disease.
SO - J Neurol 2002 Jan;249(1):110-1
UI - 11985387
AU - Patrono C; Casali C; Tessa A; Cricchi F; Fortini D; Carrozzo R;
Siciliano G; Bertini E; Santorelli FM
Missense and splice site mutations in SPG4 suggest loss-of-function in
dominant spastic paraplegia.
SO - J Neurol 2002 Feb;249(2):200-5
AD - IRCCS-Children's Hospital Bambino Gesu, Rome, Italy.
We studied nine Italian families with a pure form of autosomal dominant
spastic paraplegia (ADHSP) to assess the frequency of mutations in the
SPG4 gene. We observed marked intrafamilial variability in both
age-at-onset and clinical severity, ranging from severe congenital
presentation to mild involvement after age 55 years to healthy carriers
of the mutation after age 70. Four of nine probands harboured SPG4
mutations, We identified three new SPG4 mutations, all predicting a
loss-of-func-tion with apparently important consequences for spastin
function. RT-PCR studies predict loss-of-function as a possible
mechanism leading to spastin-related HSP. The current study expands the
spectrum of allelic variants in SPG4, confirming their pathological
significance in pure AD-HSP and suggesting implications for the presumed
function of spastin.
UI - 12039933
AU - Berry DA; Iversen ES Jr; Gudbjartsson DF; Hiller EH; Garber JE; Peshkin
BN; Lerman C; Watson P; Lynch HT; Hilsenbeck SG; Rubinstein WS; Hughes
KS; Parmigiani G
BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and
prevalence of other breast cancer susceptibility genes.
SO - J Clin Oncol 2002 Jun 1;20(11):2701-12
AD - Department of Biostatistics, University of Texas M.D. Anderson Cancer
Center, Houston, TX 77030-4009, USA. firstname.lastname@example.org
PURPOSE: To compare genetic test results for deleterious mutations of
BRCA1 and BRCA2 with estimated probabilities of carrying such mutations;
to assess sensitivity of genetic testing; and to assess the relevance of
other susceptibility genes in familial breast and ovarian cancer.
PATIENTS AND METHODS: Data analyzed were from six high-risk genetic
counseling clinics and concern individuals from families for which at
least one member was tested for mutations at BRCA1 and BRCA2.
Predictions of genetic predisposition to breast and ovarian cancer for
301 individuals were made using BRCAPRO, a statistical model and
software using Mendelian genetics and Bayesian updating. Model
predictions were compared with the results of genetic testing. RESULTS:
Among the test individuals, 126 were Ashkenazi Jewish, three were male
subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were
unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2
mutations. BRCAPRO performed well: for the 150 probands with the
smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion
testing positive was 32.7%; for the 151 probands with the largest
carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic
testing sensitivity was estimated to be at least 85%, with
false-negatives including mutations of susceptibility genes heretofore
unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for
determining the probability of carrying mutations of BRCA1 and BRCA2.
Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an
estimated 15% of mutations. In the populations studied, breast cancer
susceptibility genes other than BRCA1 and BRCA2 either do not exist, are
rare, or are associated with low disease penetrance.
UI - 12176944
AU - Trip MD; Smulders YM; Wegman JJ; Hu X; Boer JM; ten Brink JB; Zwinderman
AH; Kastelein JJ; Feskens EJ; Bergen AA
Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong
increase in the prevalence of coronary artery disease.
SO - Circulation 2002 Aug 13;106(7):773-5
AD - Department of Cardiology, Academic Medical Centre, University of
Amsterdam, Amsterdam, The Netherlands. M.D.Trip@AMC.UVA.NL
BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inborn disorder of the
connective tissue with specific skin, ocular, and cardiovascular disease
(CVD) manifestations. Recently, we and others have identified mutations
in the gene coding for the ABCC6 transporter in PXE patients with ocular
and skin involvement. In the Netherlands, as in the rest of Europe, a
particular premature truncation variant ABCC6 (R1141X) was found in a
large cohort of PXE patients. Given the association between CVD and PXE,
we hypothesized that heterozygosity of this ABCC6 mutation could also
confer an increased risk for CVD. METHODS AND RESULTS: To assess the
relationship between the frequent R1141X mutation in the ABCC6 gene and
the prevalence of premature coronary artery disease (CAD), we conducted
a case-control study of 441 patients under the age of 50 years who had
definite CAD and 1057 age- and sex-matched population-based controls who
were free of coronary disease. Strikingly, the prevalence of the R1141X
mutation was 4.2 times higher among patients than among controls (3.2%
versus 0.8%; P<0.001). Consequently, among subjects with the R1141X
mutation, the odds ratio for a coronary event was 4.23 (95% CI: 1.76 to
10.20, P= 0.001). CONCLUSION: The presence of the R1141X mutation in the
ABCC6 gene is associated with a sharply increased risk of premature CAD.
UI - 12188064
AU - Balraj P; Khoo AS; Volpi L; Tan JA; Nair S; Abdullah H
Mutation analysis of the BRCA1 gene in Malaysian breast cancer patients.
SO - Singapore Med J 2002 Apr;43(4):194-7
AD - Division of Molecular Pathology, Institute for Medical Research, Kuala
Thirty patients with early onset breast cancer or familial breast cancer
from Malaysia were analysed for germline mutation in the early onset
breast cancer I gene (BRCA1). Direct sequencing of the entire coding
region of BRCA1 identified a frameshift mutation, c.5447-5448insC
(insC5447) (codon 1776 of exon 21) in a patient aged 32 of the Malay
ethnic origin, who had no family history of breast and/or ovarian
cancer. Eight polymorphisms (2201C > T, 2430T > C, P871L, E1038G,
K1183R, 4427T > C, S1613G and IVS8-57delT) were identified in the
UI - 9752586
AU - Magnus D
Disease gene patenting: the clinician's dilemma.
SO - Camb Q Healthc Ethics 1998 Fall;7(4):433-5
AD - University of Pennsylvania's Center for Bioethics, USA.
UI - 12194197
AU - Maloney DM
Evaluation of human subject protections in schizophrenia research
conducted by the University of ... (Part I).
SO - Hum Res Rep 1999 Nov;14(11):5-6
AD - The Deem Corporation, P.O. Box 44069, Omaha, NE 68144, USA.
UI - 12191538
AU - Tercyak KP; Peshkin BN; DeMarco TA; Brogan BM; Lerman C
Parent-child factors and their effect on communicating BRCA1/2 test
results to children.
SO - Patient Educ Couns 2002 Jun;47(2):145-53
AD - Lombardi Cancer Center, Georgetown University Medical Center, 2233
Wisconsin Avenue, NW, Suite 317, Washington, DC 20007, USA.
The purpose of the present study was to evaluate the likelihood and the
effect of parent-child factors on communicating about maternal genetic
test results for breast/ovarian cancer risk. Subjects were 42 mothers
enrolled in a hereditary breast cancer research program who reported on
their interactions with 68 target children. Predictor variables
(demographic, clinical, and psychological) were assessed at baseline
after mothers participated in a comprehensive genetic
counseling/education session and provided a blood sample for BRCA1/2
mutation analysis. Maternal communication of test results to children
was assessed 1 month after mothers learned their mutation status. The
rate of disclosure to pediatric-age children was 53%. Older children
were more likely to be informed of their mothers' test results than were
younger children. Maternal disclosure of genetic test results to
children was also more likely to occur in the presence of more open
parent-child communication styles, though the act of disclosing did not
appear to impact communication style. These findings suggest that in
addition to developmental phase, family behavioral interactions and
communication styles are strongly predictive of whether or not mothers
choose to share cancer genetic risk information with their children.
UI - 11216666
AU - Loudianos G; Lovicu M; Solinas P; Kanavakis E; Tzetis M; Manolaki N;
Panagiotakaki E; Karpathios T; Cao A
Delineation of the spectrum of Wilson disease mutations in the Greek
population and the identification of six novel mutations.
SO - Genet Test 2000;4(4):399-402
AD - Ospedale Regionale per Le Microcitemie, Cagliari, Italy.
In this study, we report the further results of an ongoing project on
the delineation of the spectrum of mutations on the ATP7B gene in Wilson
disease (WD) patients of Greek origin. We have analyzed 24 additional
families and detected 16 mutations (five frameshifts, two splice site,
two nonsense, and seven missense), of which six are novel. On adding
these results to the ones already published by us, we conclude that WD
shows a marked allelic heterogeneity in the Greek population. Of the
total number of mutations so far detected, the most common eight account
for the molecular defect in 72.8% of the WD chromosomes. The most
frequent mutation is the His0169Gln, which has a frequency of 28.5%,
similar to those reported in North European populations. Using these
data, an efficient strategy of mutation screening for WD is possible in
this population, thus improving the possibility of preclinical
UI - 11476081
AU - Ockenga J; Stuhrmann M; Manns MP
Evaluation of the role of CFTR in alcohol related pancreatic disease.
SO - Gut 2001 Aug;49(2):312-3
UI - 11677941
AU - Kobayashi S; Ochiai T; Hori S; Suzuki T; Shimizu T; Gunji Y; Shimada H;
Yamamoto S; Ogawa A; Kohno Y; Sunaga M; Shimazu M; Tanaka K
Copper metabolism after living donor liver transplantation for hepatic
failure of Wilson's disease from a gene mutated donor.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1259-61
AD - Department of Academic Surgery, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8670, Japan.
There is a genetic problem in living donor liver transplantation,
involving Wilson's disease, because the majority of donors have a
kinship relationship. Recently, it was reported that the serum
ceruloplasmin level is insufficient in some persons with one allele
mutation. The recipient was a 13-year-old male child, and the donor was
a 22-year-old woman, who was his sister by a different father. The gene
analysis for Wilson's disease (ATP7B gene) was preoperatively carried
out by the amplification refractory mutation system-PCR. Homozygous and
heterozygous deletion of 2871 cytosine (C) were detected in the
recipient and donor, respectively, in the ATP7B gene. Serum
ceruloplasmin level was sufficient in the donor. The right hepatic lobe
graft was transplanted to the recipient. Immediately after the liver
transplantation, the copper metabolism improved to increase the serum
ceruloplasmin levels up to the normal range, and decrease the urinary
copper excretion. However, the serum ceruloplasmin levels gradually
decreased below the normal base line, although the urine copper levels
continued to be low without any clinical symptoms. We should perform
gene analyses and confirm the serum ceruloplasmin levels in donors
before living donor liver transplantation for Wilson's disease, to
screen for their impairment of copper metabolism. After living donor
liver transplantation for Wilson's disease, we should carefully
follow-up the transition of serum ceruloplasmin levels in the recipient.
UI - 11758609
AU - Witt H; Landt O
Rapid detection of the Wilson's disease H1069Q mutation by melting curve
analysis with the LightCycler.
SO - Clin Chem Lab Med 2001 Oct;39(10):953-5
AD - Department of Paediatrics, Charite, Humboldt University, Berlin,
Wilson's disease is an inherited autosomal recessive disorder of copper
transport characterized by progressive copper accumulation in the liver
and the central nervous system. The disease is caused by mutations in
the ATP7B gene. Although many different mutations in this gene were
described, a substitution of a histidine by a glutamine residue at codon
1069 (H1069Q) accounts for approximately 30-60% of all mutations in
Caucasian patients. We describe a DNA-based method using fluorescence
resonance energy transfer probes on the LightCycler for rapid
determination of the common H1069Q mutation in the ATP7B gene. We
screened 53 patients with Wilson's disease for the H1069Q mutation by
the melting curve analysis. The reliability and discriminating power of
this technique were documented by comparing results of the LightCycler
assay with direct DNA sequencing. The protocol allows genotyping of 30
samples in less than 1 hour without a need for restriction enzyme
digestion or gel electrophoresis.
UI - 11920200
AU - Badens C; Martinez di Montemuros F; Thuret I; Michel G; Mattei JF;
Cappellini MD; Lena-Russo D
Molecular basis of haemoglobinopathies and G6PD deficiency in the
SO - Hematol J 2000;1(4):264-8
AD - Centre d'Enseignement et de Recherche en Genetique Medicale, Hopital
d'enfants de la Timone, Marseilles, France. email@example.com
INTRODUCTION: The Comoro archipelago is characterised by a high
prevalence of red cell genetic disorders such as G6PD deficiency and
haemoglobinopathies, being a region endemic for malaria. Over the last
15 years, the city of Marseilles in France has become the main
destination for Comorian immigrants. This Comorian community includes
patients with sickle cell disease, sickle cell/beta-thalassaemia trait,
thalassaemias and G6PD deficiency. MATERIALS AND METHODS: Allele
frequencies for haemoglobin S, beta-thalassaemia and G6PD deficiency
were determined from neonatal and prenatal screenings of the Comorian
community. Haemoglobin fractions were detected by
isoelectrofocalisation, and the quantitation of HbS, HbA, HbA(2) and HbF
was performed by cation exchange high performance liquid chromatography.
The molecular study involved 31 alleles carrying the betaS mutation (Cd
6 [A-->T]), six beta-thalassaemic alleles and 17 G6PD-deficient alleles,
selected from a group of carriers or affected subjects. RESULTS: Allele
frequencies were 3% for haemoglobin S, 1% for beta-thalassaemia trait
and 9.5% for G6PD deficiency. Molecular analysis had revealed that the
African alleles are predominant, being present in almost all the
subjects studied. Mediterranean alleles were found for all the
beta-thalassaemia mutations and for three G6PD chromosomes out of 17.
CONCLUSION: These data are consistent with the mixed Arab and African
origin of the population of the Comoro Islands, and are of clinical
interest in prenatal and newborn screening plans.
UI - 12111613
AU - Brugnoni R; Leone M; Rigamonti A; Moranduzzo E; Cornelio F; Mantegazza
R; Bussone G
Is the CACNA1A gene involved in familial migraine with aura?
SO - Neurol Sci 2002 Apr;23(1):1-5
AD - Department of Neuromuscular Diseases, C. Besta National Neurological
Institute, Milan, Italy.
The discovery of mutations in the neural calcium channel (CACNA1A) gene
in familial hemiplegic migraine (FHM), variant of migraine with aura,
led to the suggestion that this gene might be involved in familial
migraine with aura (FMA). We investigated whether the mutations in FHM
are present in FMA patients, analyzing genomic DNA by PCR, single
stranded conformation polymorphism, sequencing and restriction enzyme.
No mutations were found. A known polymorphism (5682-14C>T) was found in
exon 36. These findings suggest that the mutations found in FHM and the
other known mutations of the CACNA1A gene are not the genetic basis of
FMA. Genetic alterations in FMA patients may be localized on chromosome
19 but not in the CACNA1A exons we investigated.
UI - 12111614
AU - Cevoli S; Pierangeli G; Monari L; Valentino ML; Bernardoni P; Mochi M;
Cortelli P; Montagna P
Familial hemiplegic migraine: clinical features and probable linkage to
chromosome 1 in an Italian family.
SO - Neurol Sci 2002 Apr;23(1):7-10
AD - Institute of Clinical Neurology, University of Bologna Medical School,
Via Ugo Foscolo 7, I-40123 Bologna, Italy.
We describe an Italian family with familial hemiplegic migraine (FHM),
subtle cerebellar signs and probable linkage to chromosome 1. FHM is
genetically heterogeneous; in about 50% of families it is caused by
mutations within the CACNA1A gene on chromosome 19. Linkage to 1q31 and
1g21-23 has also been established. Other families do not link either to
chromosome 19 or 1. Chromosome 19-linked FHM may display nystagmus and
cerebellar ataxia. Affected family members were neurologically examined;
linkage analysis was performed with markers for chromosomes 19p13,
1q21-23, and 1q32. Five family members had hemiplegic migraine, and 3
displayed additional cerebellar signs (scanning speech and nystagmus).
In 1 patient, episodes of hemiplegic migraine triggered by mild head
trauma. Epilepsy and mental retardation were also found in 1 affected
relative each. Lod scores for linkage to 19p13 were negative, while the
maximum two-point lod score was 1.81 to 1q21-23. This family with FHM
and associated subtle cerebellar signs, epilepsy and mental retardation
showed probable linkage to 1q21-23.
UI - 12167832
AU - Williamson R; Duncan R
DNA testing for all.
SO - Nature 2002 Aug 8;418(6898):585-6
AD - Murdoch Children's Research Institute, University of Melbourne, Royal
Children's Hospital, Parkville, Victoria, Australia.
UI - 12236245
AU - Bowers NR
Meeting the standard of genetic nursing care.
SO - J Spec Pediatr Nurs 2002 Jul-Sep;7(3):123-6
AD - University of Cincinnati, OH, USA. Nancy.Bowers@uc.edu
UI - 12239538
AU - Bowyer A
Could we trust every future government?
SO - Nature 2002 Sep 19;419(6904):247
UI - 12362848
AU - Nilbert M; Gronberg H; Lindblom A
[Essential to discover hereditary colorectal and endometrial cancer.
Mutations in "HNPCC individuals" can cause several different tumors]
SO - Lakartidningen 2002 Aug 22;99(34):3296-300
AD - Onkologiska kliniken, Universitetssjukhuset i Lund.
Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is one of our most
common hereditary cancer syndromes and confers an increased risk for
several tumor types, with the greatest lifetime risks being for
colorectal cancer and endometrial cancer. Hereditary mutations in one of
several mismatch-repair (MMR) genes cause the syndrome, and 39 such
mutations, involving the genes MLH1, MSH2 and MSH6, have been been
characterized in Sweden. Screening programs for HNPCC have been shown to
be cost-effective and to prevent cancer. Identification of HNPCC
individuals thus allows prevention of additional tumors in the patient
as well as in the family.
UI - 10222510
AU - Rieger PT; Pentz RD
Genetic testing and informed consent.
SO - Semin Oncol Nurs 1999 May;15(2):104-15
AD - University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
OBJECTIVES: To discuss unique issues related to cancer predisposition
genetic testing and informed consent. DATA SOURCES: Published
professional articles, review articles, research articles, clinical
practice, position statements, websites, and textbooks. CONCLUSIONS: The
discovery of germline mutations that confer a predisposition for the
development of cancer will continue. The provision of adequate
information is central to the process of genetic counseling and testing
so that individuals may give informed consent and make choices
appropriate to their own specific circumstances. IMPLICATIONS FOR
NURSING PRACTICE: The use of genetic information for the management of
cancer will impact the practice of all oncology nurses in the coming
years. Knowledge of genes that predispose for cancer and standards that
delineate essential components of quality care during the informed
consent process is vital.
UI - 11967008
AU - Rossetti S; Chauveau D; Walker D; Saggar-Malik A; Winearls CG; Torres
VE; Harris PC
A complete mutation screen of the ADPKD genes by DHPLC.
SO - Kidney Int 2002 May;61(5):1588-99
AD - Division of Nephrology, Mayo Clinic and Foundation, Rochester, Minnesota
BACKGROUND: Genetic analysis is a useful diagnostic tool in autosomal
dominant polycystic kidney disease (ADPKD), especially when imaging
results are equivocal. However, molecular diagnostics by direct mutation
screening has proved difficult in this disorder due to genetic and
allelic heterogeneity and complexity of the major locus, PKD1. METHODS:
A protocol was developed to specifically amplify the exons of PKD1 and
PKD2 from genomic DNA as 150 to 450 bp amplicons. These fragments were
analyzed by the technique of denaturing high-performance liquid
chromatography (DHPLC) using a Wave Fragment Analysis System
(Transgenomics) to detect base-pair changes throughout both genes.
DHPLC-detected changes were characterized by sequencing. RESULTS: Cost
effective and sensitive mutation screening of the entire coding regions
of PKD1 and PKD2 by DHPLC was optimized. All base-pair mutations to
these genes that we previously characterized were detected as an altered
DHPLC profile. To assess this method for routine diagnostic use, samples
from a cohort of 45 genetically uncharacterized ADPKD patients were
analyzed. Twenty-nine definite mutations were detected, 26 PKD1, 3 PKD2
and a further five possible missense mutations were characterized
leading to a maximal detection rate of 76%. A high level of polymorphism
of PKD1 also was detected, with 71 different changes defined. The
reproducibility of the DHPLC profile enabled the recognition of many
common polymorphisms without the necessity for re-sequencing.
CONCLUSIONS: DHPLC has been demonstrated to be an efficient and
effective means for gene-based molecular diagnosis of ADPKD.
Differentiating missense mutations and polymorphisms remains a
challenge, but family-based segregation analysis is helpful.
UI - 12096298
AU - Stacey D; DeGrasse C; Johnston L
Addressing the support needs of women at high risk for breast cancer:
evidence-based care by advanced practice nurses.
SO - Oncol Nurs Forum 2002 Jul;29(6):E77-84
AD - Ottawa Health Research Institute, University of Ottawa, Ontario, Canada.
PURPOSE/OBJECTIVES: To identify support needs of women at high risk for
breast cancer and enhance an evidence-based service. DESIGN: Descriptive
study. SETTING: A comprehensive, breast-health service for high-risk
women. SAMPLE: 97 high-risk women with a 1.66% or greater five-year risk
of breast cancer, atypical hyperplasia, lobular carcinoma in situ, or
positive genetic screen. METHODS: A self-assessment questionnaire
completed previsit and a satisfaction survey completed postvisit. MAIN
RESEARCH VARIABLES: Women's perceived informational, emotional, and
decisional support needs, current self-care practices, and satisfaction
with the service provided. FINDINGS: Women under age 50 (n = 54) wanted
information on breast cancer screening, risk of breast cancer, lifestyle
options to lower risk, and hormone replacement therapy; older women (n =
43) wanted information on risk of breast cancer, lifestyle options,
breast cancer screening, and chemoprevention. More than 75% of all women
wanted information to help them make decisions on breast cancer
prevention options, benefits, and risks. The satisfaction survey (N =
61) revealed that most women's needs were met. CONCLUSIONS: Support
needs were consistent with the literature that focused primarily on
younger women seeking genetic counseling. Proactive planning assisted
with addressing the needs of these women. IMPLICATIONS FOR NURSING: A
previsit questionnaire facilitates individualized proactive planning
before the visit. However, further assessment of self-care practices and
emotional needs is required. Interventions should evaluate outcomes,
such as accurate risk perception, lifestyle changes, screening