Abstract:
:The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Spurdle AB,Greville-Heygate S,Antoniou AC,Brown M,Burke L,de la Hoya M,Domchek S,Dörk T,Firth HV,Monteiro AN,Mensenkamp A,Parsons MT,Radice P,Robson M,Tischkowitz M,Tudini E,Turnbull C,Vreeswijk MP,Walker LC,Tavtigidoi
10.1136/jmedgenet-2018-105872subject
Has Abstractpub_date
2019-06-01 00:00:00pages
347-357issue
6eissn
0022-2593issn
1468-6244pii
jmedgenet-2018-105872journal_volume
56pub_type
杂志文章abstract:BACKGROUND:Non-syndromic isolated cleft lip with or without cleft palate (NCL/P) is a common congenital anomaly in humans, the aetiology of which is complex and associated with both genetic and environmental factors. It has been reported that maternal nutritional factors are likely to play a major role in development o...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2009.070029
更新日期:2010-12-01 00:00:00
abstract::Intelligence levels and intelligence profiles were investigated in 52 members of a large family with the fragile X syndrome. The mental abilities were evaluated by the three Wechsler intelligence tests (WAIS, WISC-R, and WPPSI). Chromosomal and psychological data were then compared. In 22 non-retarded fra(X) negative ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.24.1.32
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer's disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investiga...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2005.033936
更新日期:2006-05-01 00:00:00
abstract::Chromosome and enzyme determinations were performed in 250 pregnancies between the 7th and the 12th week of gestation. The majority of the tests were performed for risk of chromosomal abnormalities and 75% of the women were 35 years old or more. We describe a chorionic villi sampling (CVS) technique which proved to be...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.22.2.92
更新日期:1985-04-01 00:00:00
abstract::Clinical and radiographic evaluation of an infant boy and his father revealed findings suggesting a new variant of spondylometaphyseal dysplasia with an apparently autosomal dominant mode of inheritance. The main clinical findings included short stature and marked ligamentous laxity in the infant. X-ray findings inclu...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.19.2.104
更新日期:1982-04-01 00:00:00
abstract:BACKGROUND:Alport syndrome is a clinically heterogeneous, progressive nephropathy caused by mutations in collagen IV genes, namely COL4A3 and COL4A4 on chromosome 2 and COL4A5 on chromosome X. The wide phenotypic variability and the presence of incomplete penetrance suggest that a simple Mendelian model cannot complete...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2014-102822
更新日期:2015-03-01 00:00:00
abstract::This is a study of 138 index patients with retinitis pigmentosa (RP) and their families, in which the selection of index patients was solely on the basis of their residence in Birmingham. Clinical analysis showed that severe disease was as likely to indicate dominant or non-genetic RP as to indicate recessive disease,...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.21.6.421
更新日期:1984-12-01 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:BACKGROUND:Warfarin is a mainstay of therapy for conditions associated with an increased risk of thromboembolic events. However, the use of this common agent is fraught with complications and little is known regarding inter-individual variation in warfarin response. OBJECTIVE:We tested for association between single n...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2005.040410
更新日期:2006-09-01 00:00:00
abstract::Adrenal hypoplasia congenita (AHC) can occur due to deletions or mutations in the DAX 1 (NR0B1) gene on the X chromosome (OMIM 300200). This form of AHC is therefore predominantly seen in boys. Deletion of the DAX 1 gene can also be part of a larger contiguous deletion including the centromeric dystrophin and glycerol...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2007.055129
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Pulmonary fibrosis is a complex disease for which the predisposing genetic variants remain unknown. In a prior study, susceptibility to bleomycin induced pulmonary fibrosis was mapped to loci Blmpf1 and Blmpf2 on chromosomes 17 and 11, respectively, in a C57BL/6J (B6, susceptible) and C3Hf/KAM (C3H, resistan...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2004.027938
更新日期:2005-06-01 00:00:00
abstract::A family is described in which 2 sibs had similar congenital abnormalities. Chromosome investigation of the mother and another child disclosed they were carriers of a translocation t(18;21)(q21;q22). The karyotype of one of the abnormal infants was determined and was found to be consistent with partial trisomy 18,46,X...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.15.2.148
更新日期:1978-04-01 00:00:00
abstract::Treacher Collins syndrome is an autosomal dominant disorder of facial development, the features of which include conductive hearing loss and cleft palate. In the current investigation, linkage analysis has been used to make first trimester diagnostic predictions in a pregnancy at high risk of producing an affected chi...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.33.7.603
更新日期:1996-07-01 00:00:00
abstract::Molecular genetic investigation of a female infant with Beckwith-Wiedemann syndrome (BWS) showed loss of IGF2 imprinting but no evidence of uniparental disomy. In addition, a deletion of chromosome 18q22.1 was identified in this infant without clinical features of 18q-syndrome (microcephaly, short stature, hypotonia)....
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.2.162
更新日期:1998-02-01 00:00:00
abstract::A baby with a 46,XY,r(20) karyotype is described. The distinguishing features of this rare chromosome anomaly are analysed in the light of the suggested r(20) syndrome. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.24.6.375
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:Graves' disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). METHODS:We re-examined the X chromosome data from our...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2013-101595
更新日期:2013-07-01 00:00:00
abstract:INTRODUCTION:We report a 34-year-old Japanese female with a Silver-Russell syndrome (SRS)-like phenotype and a mosaic Turner syndrome karyotype (45,X/46,XX). METHODS/RESULTS:Molecular studies including methylation analysis of 17 differentially methylated regions (DMRs) on the autosomes and the XIST-DMR on the X chromo...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2010.079343
更新日期:2010-11-01 00:00:00
abstract::We report a new case of Rubinstein-Taybi syndrome with a hypoplastic right kidney, persistent pulmonary hypertension, and mitral valve regurgitation. Other pertinent features included broad thumbs, broad big toes, syndactyly of the third and fourth fingers bilaterally, beaked nose, broad columella of the nose, patent ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.29.9.669
更新日期:1992-09-01 00:00:00
abstract::Cleidocranial dysplasia (CCD) (MIM 119600) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene has been mapped to chromosome 6p21 within a region containing CBFA1, ...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:HLA-DRB1 is the strongest susceptibility gene to rheumatoid arthritis (RA). HLA-DRB1 alleles showed significant non-additive and interactive effects on susceptibility to RA in the European population, but these effects on RA susceptibility should vary between populations due to the difference in allelic dist...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2017-104779
更新日期:2017-12-01 00:00:00
abstract::Two half sibs with bilateral complete cleft lip and complete cleft of the palate associated with ectrodactyly of the hands and feet, born to the same phenotypically normal mother, are reported. The younger of the two sibs also has dominantly inherited tremors (also referred to as essential heredofamilial tremors) as d...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.18.5.394
更新日期:1981-10-01 00:00:00
abstract:BACKGROUND:Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathwa...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2012-101016
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Cole-Carpenter syndrome (CCS) is commonly classified as a rare Osteogenesis Imperfecta (OI) disorder. This was following the description of two unrelated patients with very similar phenotypes who were subsequently shown to have a heterozygous missense mutation in P4HB. OBJECTIVES:Here, we report a 3-year ol...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2017-104899
更新日期:2018-03-01 00:00:00
abstract::Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome associated with a characteristic pattern of visceromegaly and predisposition to childhood tumours. BWS is a genetically heterogeneous disorder; most cases are sporadic but approximately 15% are familial and a small number of BWS patients have cytoge...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.5.353
更新日期:1997-05-01 00:00:00
abstract::Our primary objective was to estimate, by one year and five year intervals, maternal age specific risk rates for Down syndrome among whites and among other races from two different populations, metropolitan Atlanta and south west Ohio, using live birth and prenatally diagnosed cases ascertained during 1970-1989. The f...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.6.482
更新日期:1998-06-01 00:00:00
abstract::The association of maternal uniparental disomy for chromosome 7 and postnatal growth failure has been reported in four cases and suggests the presence of genomic imprinting of one or more growth related genes on chromosome 7. However, in the reported cases, the possibility of homozygosity for a recessive mutation coul...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.32.11.871
更新日期:1995-11-01 00:00:00
abstract::An estimated 15-50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivit...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmedgenet-2011-100386
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The melanocortin-4-receptor gene (MC4R) is part of the melanocortinergic pathway that controls energy homeostasis. In a recent meta-analysis, the MC4R V103I (rs2229616) polymorphism was shown to be associated with body weight regulation. Although no functional differences between the isoleucine comprising re...
journal_title:Journal of medical genetics
pub_type: 信件
doi:10.1136/jmg.2004.027011
更新日期:2005-04-01 00:00:00
abstract::A family is reported which a diabetic woman gave birth to two children with the caudal regression anomalad (CRA). There were no obvious genetic factors. This is the first reported familial case of CRA with maternal diabetes. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.16.1.17
更新日期:1979-02-01 00:00:00
abstract::Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common form of autosomally inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an insidious onset of bilateral visual loss and they characteristically have tempor...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.35.10.793
更新日期:1998-10-01 00:00:00