Abstract:
BACKGROUND:The clinical phenotype of CDH1 pathogenic variant carriers has mostly been studied in families that fulfil criteria of hereditary diffuse gastric cancer (HDGC). We aimed at determining cancer phenotype and cancer risk estimation among families with CDH1 pathogenic variants not selected by HDGC clinical criteria. METHODS:Patients were all consecutively identified CDH1 pathogenic variant carriers from a clinical laboratory tested with multigene panel testing and from an academic cancer genetics programme. Clinical and demographic features, cancer phenotypes and genotype-phenotype correlations were determined among CDH1 families. Age-specific cumulative cancer risks (penetrance) were calculated based on 38 families with available pedigrees. RESULTS:Within the 113 CDH1 pathogenic variant probands and 476 relatives, 113 had gastric cancer, 177 breast cancer and 196 other cancers. Mean age at diagnosis was 47 for gastric and 54 for breast cancer. Forty-six per cent fulfilled criteria of HDGC. While 36% of families had both gastric and breast cancers, 36% had breast but no gastric cancers and 16% had gastric but not breast cancers. Cumulative risk of cancer by age 80 was 37.2% for gastric and 42.9% for breast cancer. CONCLUSION:In unselected CDH1 pathogenic variant carrier families, gastric cancer risks were lower and age at diagnosis higher than previously reported in families pre-selected for HDGC criteria. A substantial proportion of families did not present with any gastric cancers and their cancers were limited to breast. Thus, clinical criteria for CDH1 testing should be widened, including breast cancer families only, and a consideration for delayed prophylactic gastrectomy/surveillance should be evaluated.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Xicola RM,Li S,Rodriguez N,Reinecke P,Karam R,Speare V,Black MH,LaDuca H,Llor Xdoi
10.1136/jmedgenet-2019-105991subject
Has Abstractpub_date
2019-12-01 00:00:00pages
838-843issue
12eissn
0022-2593issn
1468-6244pii
jmedgenet-2019-105991journal_volume
56pub_type
杂志文章abstract::Primary ciliary dyskinesia is an autosomal recessive condition characterised by chronic sinusitis, bronchiectasis, and subfertility. Situs inversus occurs in 50% of cases (Kartagener syndrome). It has an estimated incidence of 1 in 20 000 live births. The clinical phenotype is caused by defective ciliary function asso...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.37.4.241
更新日期:2000-04-01 00:00:00
abstract::Published reports on the sex ratio of spina bifida have been reviewed. With one exception, there seems to be no evidence of variation in the sex ratio of spina bifida. In particular, unlike anencephaly, the sex ratio of spina bifida seems to be unrelated to the prevalence of the malformation: this (M/(M+F)) is of the ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.16.5.384
更新日期:1979-10-01 00:00:00
abstract::Three hundred and fifty pregnancies were monitored by transabdominal amniocentesis in the fourteenth to sixteenth week of gestation followed by karyotyping or biochemica assays of cultured amniotic fluid cells and analysis of alpha-fetoprotein in the amniotic fluid supernatant. The pregnancy was interrupted in 36 case...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.13.3.182
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abstract::The cap capacity in nine Duchenne muscular dystrophy (DMD) patients and in 23 healthy male subjects (14 adults and nine neonates) has been investigated by inducing capping of HLA molecules. The evaluation of capping percentages ranged in healthy controls from 44 to 61 with a mean value of 53.39 +/- 4.89, while DMD pat...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.21.3.182
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abstract::Costovertebral dysplasia comprises multiple malformations of the vertebrae and ribs, with a characteristic clinical picture of short trunk dwarfism, short neck, scoliosis, and rib cage deformity. We describe two sibs with the syndrome who are presumed to represent the autosomal recessive form of the disorder. One sib ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.20.6.441
更新日期:1983-12-01 00:00:00
abstract::It has recently been emphasised that a subset of patients with type 2 Gaucher disease die in the neonatal period. This report describes an Afghani family with two conceptuses having severe, prenatally detected Gaucher disease. Mutational analysis showed that the family carried a known complex allele which included mut...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.33.2.132
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abstract::The impact of information-guidance type of genetic counseling was evaluated for the family planning of 2082 consultands. The understanding of the risks, parental decision, and the number of induced and spontaneous abortions were evaluated by the use of questionnaires. The stillbirths, livebirths, infant deaths, and ba...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.18.2.91
更新日期:1981-04-01 00:00:00
abstract::We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2007.057042
更新日期:2008-07-01 00:00:00
abstract:INTRODUCTION:Medullary cystic kidney disease 2 (MCKD2) and familial juvenile hyperuricaemic nephropathy (FJHN) are both autosomal dominant renal diseases characterised by juvenile onset of hyperuricaemia, gout, and progressive renal failure. Clinical features of both conditions vary in presence and severity. Often defi...
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pub_type: 杂志文章
doi:10.1136/jmg.39.12.882
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Limb-girdle muscular dystrophy type R1 (LGMDR1) can be caused by recessive CAPN3 mutations accounting for the majority of LGMD. To date, no systemic evaluation has been performed to analyse the detrimental and normal mutations on CAPN3 and its hotspots. METHODS:CAPN3 variants (n=112) from a total of 124 pat...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2020-107159
更新日期:2020-09-29 00:00:00
abstract::We have performed an extensive analysis of TP53 in 474 French families suggestive of Li-Fraumeni syndrome (LFS), including 232 families fulfilling the Chompret criteria. We identified a germline alteration of TP53 in 82 families (17%), in 67/232 of the families fulfilling the Chompret criteria (29%) and in 15/242 whic...
journal_title:Journal of medical genetics
pub_type: 信件
doi:10.1136/jmg.2008.057570
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:The genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear. METHODS:Two Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2020-107042
更新日期:2020-09-08 00:00:00
abstract:BACKGROUND:Fanconi anaemia is a heterogeneous genetic disease, where 12 complementation groups have been already described. Identifying the complementation group in patients with Fanconi anaemia constitutes a direct procedure to confirm the diagnosis of the disease and is required for the recruitment of these patients ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2006.044719
更新日期:2007-04-01 00:00:00
abstract::MWS is a multiple congenital anomaly syndrome, first clinically delineated by Mowat et al in 1998. Over 45 cases have now been reported. All patients have typical dysmorphic features in association with severe intellectual disability, and nearly all have microcephaly and seizures. Congenital anomalies, including Hirsc...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.40.5.305
更新日期:2003-05-01 00:00:00
abstract::Fucosidosis is a rare, autosomal recessive, lysosomal storage disease, resulting from a deficiency of the enzyme alpha-fucosidase (EC 3.2.1.51). It is characterised clinically by progressive mental and motor deterioration, growth retardation, coarse facies, and often recurrent infections, but the course of the disease...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.30.3.218
更新日期:1993-03-01 00:00:00
abstract::The BglII polymorphism near the constant region of the T cell receptor beta chain (TCR c beta) has been investigated in normal controls, patients with cystic fibrosis (CF), and CF carriers. A significant increase was found in the frequency of the 10.0:9.2 kb heterozygous genotype in the CF carrier group (71%) as compa...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.26.7.431
更新日期:1989-07-01 00:00:00
abstract::Twenty-six patients with Gaucher's disease diagnosed in the United Kingdom and two obligate carriers, all of non-Jewish origin, were screened for the two common disease causing mutations and two rarer mutations in the glucocerebrosidase gene. These mutations are referred to as N370S, L444P, Ins84G, and 1066 + 1G-->A, ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.30.4.280
更新日期:1993-04-01 00:00:00
abstract::We have analysed 40 marker loci on 13 chromosomes for linkage with Marfan syndrome. None of the loci was linked to the Marfan syndrome locus at theta = 0.00. This study provides a basis for an exclusion map and for further collaboration in mapping of the locus. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.27.2.86
更新日期:1990-02-01 00:00:00
abstract:BACKGROUND:Primary ovarian insufficiency (POI) affects 1% of women under 40 years and is a public health problem. The genetic causes of POI are highly heterogeneous with isolated or syndromic forms. Recently, variants in genes involved in DNA repair have been shown to cause POI. Notably, syndromic POI with Fanconi anae...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2019-106672
更新日期:2020-06-01 00:00:00
abstract::An apparently autosomal recessive syndrome of congenital renal tubular dysplasia and skull ossification defects is described in five infants from two separate, consanguineous, Pakistani Muslim kindreds. The clinical, pathological, and radiological features are similar to the phenotype associated with fetal exposure to...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.7.541
更新日期:1997-07-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.28.4.252
更新日期:1991-04-01 00:00:00
abstract::The features of a child with osteogenesis imperfecta type III (OI III) resulting from the heterozygous substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen were studied. He was born at term with the clinical features of severe OI, including deep grey-blue sclerae. He had severe ost...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.33.3.193
更新日期:1996-03-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2007.051672
更新日期:2007-11-01 00:00:00
abstract::Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 are responsible for a subset of the muscular dystrophies. In this study we aim to characterise the nature and frequency of abnormalities of these proteins in an Australian population and to formulate an investigative algorithm to aid in approaching the ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.5.379
更新日期:1998-05-01 00:00:00
abstract::Glucocerebroside beta-glucosidase (glucocerebrosidase) activity was determined from peripheral blood lymphocytes and cultured skin fibroblasts of eight full sibs in a French-Canadian family at risk for Gaucher disease, an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. The di...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.25.5.322
更新日期:1988-05-01 00:00:00
abstract::X linked spondyloepiphyseal dysplasia (SED) is caused by a growth defect of the vertebral bodies leading to characteristic changes in the vertebral bodies and a short trunk. The gene responsible for this disorder has previously been mapped to Xp22, with a maximum likelihood location between markers DXS16 and DXS92. We...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.33.5.432
更新日期:1996-05-01 00:00:00
abstract::Rubinstein-Taybi syndrome (RTS) is a well delineated multiple congenital anomaly syndrome characterised by mental retardation, broad thumbs and toes, short stature, and specific facial features. The recent localisation of the disorder to 16p13.3 and subsequent identification of a submicroscopic deletion of this region...
journal_title:Journal of medical genetics
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doi:10.1136/jmg.34.3.203
更新日期:1997-03-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.14.3.194
更新日期:1977-06-01 00:00:00
abstract::An interstitial deletion of the region q22.1-->q22.3 of chromosome 14 is described in a child with bilateral anophthalmia, dysmorphic features including micrognathia, small tongue, and high arched palate, developmental and growth retardation, undescended testes with a micropenis, and hypothyroidism. Interstitial delet...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
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更新日期:1993-03-01 00:00:00
abstract::A syndrome of brachydactyly (absence of some middle or distal phalanges), aplastic or hypoplastic nails, symphalangism (ankylois of proximal interphalangeal joints), synostosis of some carpal and tarsal bones, craniosynostosis, and dysplastic hip joints is reported in five members of an Italian family. It may represen...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.13.5.394
更新日期:1976-10-01 00:00:00