Abstract:
:21-hydroxylase deficiency is a recessively inherited disorder of steroidogenesis, resulting from mutations in the CYP21 gene. This 3.5 kb gene and a highly related CYP21P pseudogene reside on tandemly duplicated 30 kb segments of DNA in the class III HLA region, and the great majority of pathogenic mutations result from sequence exchanges involving the duplicated units. We now describe a comprehensive survey of CYP21 mutations in the British population, encompassing a screen for 17 different mutations in a total of 284 disease chromosomes. The most common mutations were as follows: large scale deletions/conversions (45% of the affected chromosomes), the intron 2 splice mutation (30.3%), R357W (9.8%), and I172N (7.0%). Mutations were detected in over 92% of the chromosomes examined, suggesting that accurate DNA based diagnosis is possible in most cases using the described strategy. In order to extend highly accurate prenatal diagnosis to all families where samples are available from a previously affected child, we have developed a linkage analysis approach using novel, highly informative microsatellite markers from the class III HLA region.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Lako M,Ramsden S,Campbell RD,Strachan Tkeywords:
subject
Has Abstractpub_date
1999-02-01 00:00:00pages
119-24issue
2eissn
0022-2593issn
1468-6244journal_volume
36pub_type
杂志文章abstract::Fragile X syndrome is the major cause of inherited mental retardation. The molecular basis for the expression of the fragile X phenotype is the expansion of an unstable CGG repeat element which inhibits transcription of the FMR1 gene. The fragile X syndrome shows great diversity in its phenotype as well as in its cyto...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.32.11.907
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:Schneckenbecken dysplasia (SBD) is an autosomal recessive lethal skeletal dysplasia that is classified into the severe spondylodysplastic dysplasias (SSDD) group in the international nosology for skeletal dysplasias. The radiological hallmark of SBD is the snail-like configuration of the hypoplastic iliac bo...
journal_title:Journal of medical genetics
pub_type: 信件
doi:10.1136/jmg.2008.065201
更新日期:2009-08-01 00:00:00
abstract::Four different Waardenburg syndromes have been defined based upon observed phenotypes. These syndromes are responsible for approximately 2% of subjects with profound congenital hearing loss. At present, Waardenburg syndromes have not been mapped to particular human chromosomes. One or more of the mouse mutant alleles,...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.27.10.618
更新日期:1990-10-01 00:00:00
abstract::In an attempt to relate the age at onset of Huntington's disease to parental factors, the effects of parental onset-age (Po) and the age of the transmitting parent at the birth of a subsequently affected child (Pc) have been examined in a sample of cases ascertained from Victorian kindreds. There was a significant pos...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.12.1.64
更新日期:1975-03-01 00:00:00
abstract::A 10 1/2 year old female with skeletal abnormalities was referred for genetic consultation because of learning disabilities and a suggestion of 'Turner-like' stigmata. Cytogenetic analysis revealed a paracentric inversion of an X(q13.1q26.1) chromosome. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.22.2.140
更新日期:1985-04-01 00:00:00
abstract::Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, popu...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmedgenet-2015-103132
更新日期:2016-01-01 00:00:00
abstract::G band cytogenetic analysis often leads to the discovery of unbalanced karyotypes that require further characterisation by molecular cytogenetic studies. In particular, G band analysis usually does not show the chromosomal origin of small marker chromosomes or of a small amount of extra material detected on otherwise ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::This report presents the detection of a heterozygous deletion at chromosome 12q14 in three unrelated patients with a similar phenotype consisting of mild mental retardation, failure to thrive in infancy, proportionate short stature and osteopoikilosis as the most characteristic features. In each case, this interstitia...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2006.047860
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines. OBJECTIVES:Our study aimed to give a complete description of our TSC adult coh...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2019-106607
更新日期:2021-01-01 00:00:00
abstract::Chromosome analysis using conventional staining, G banding, and, after BUdR incorporation, two R banding methods, one using Hoechst and one acridine orange, were performed on lymphocytes from a pair of female monozygotic twins. The culture conditions were designed to show the presence of the fragile X (q27-28) which h...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.22.2.85
更新日期:1985-04-01 00:00:00
abstract::Ten useful two allele restriction fragment length polymorphisms of the low density lipoprotein receptor gene were used for haplotype analysis in 45 unrelated familial hypercholesterolaemic (FH) patients, 60 normal controls, and 32 FH homozygotes, all of whom were white Afrikaners. Pedigree analysis in 27 informative h...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.26.4.255
更新日期:1989-04-01 00:00:00
abstract::We have reviewed published reports on patients with segmental aneusomy for chromosome 1p36 to help geneticists and other health professionals in the recognition of this emerging chromosomal syndrome. Terminal deletions of the short arm of chromosome 1 are associated with hypotonia and developmental delay (usually seve...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
abstract::Sorsby fundus dystrophy is an autosomal dominant disorder which both clinically and histopathologically bears striking similarities to age related macular degeneration, one of the leading causes of blindness in the developed world. Recent studies have suggested a genetic localisation of the disease to chromosome 22q i...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.32.3.240
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:Multiple morphological abnormalities of the sperm flagella (MMAF) is a kind of severe teratozoospermia. Patients with the MMAF phenotype are infertile and present aberrant spermatozoa with absent, short, coiled, bent and/or irregular flagella. Mutations in several genes can explain approximately 30%-50% of M...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2018-105952
更新日期:2019-10-01 00:00:00
abstract::A 13 year old girl was referred with congenital microcephaly, developmental delay, a prominent nose, highly arched palate, and an apparently low set left ear. She was found to have a pericentric inversion of one chromosome 7 and a ring chromosome 8, 46,XX,inv(7) (pter----p22::q11.23----p22::q11.23----qter), r(8) (p23q...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.29.1.66
更新日期:1992-01-01 00:00:00
abstract::We report concordant male monozygotic twins with congenital short femur (proximal focal femoral deficiency) and discuss the aetiological implications. Coincidentally, they and their father have benign familial macrocephaly. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.23.4.363
更新日期:1986-08-01 00:00:00
abstract:BACKGROUND:We have previously described an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia (MED), and distinctive facies in a large, extended Omani family. The MED observed seems to be part of a larger malformation syndrome, since both craniofacial and central nervous system changes were pre...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.38.6.369
更新日期:2001-06-01 00:00:00
abstract::Parkinson's disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic marker...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmedgenet-2017-105047
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:Limb development is a complex process requiring proper spatio-temporal expression of a network of limb specific morphogens. Grem1 and Fmn1 play an important role in mouse and chick limb development. The mouse limb deformity (ld) phenotype with digit reduction, syndactyly, radio-ulnar synostosis, variable ren...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2009.073833
更新日期:2010-08-01 00:00:00
abstract::Several mutations in the extracellular matrix protein matrilin-3 cause a heterogeneous disease spectrum affecting skeletal tissues. We introduced three disease causing point mutations leading to single amino acid exchanges (R116W, T298M, C299S) in matrilin-3 and expressed the corresponding proteins in primary articula...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2004.029462
更新日期:2005-10-01 00:00:00
abstract::Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thi...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:Heterozygous germline PMS2 variants are responsible for about 5% of Lynch syndrome (LS) but their prevalence is most likely underestimated because of complicated routine screening caused by highly homologous pseudogenes. Consequently, there is limited knowledge on the implication of the PMS2 gene in LS. MET...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2019-106256
更新日期:2020-07-01 00:00:00
abstract::The structure of the locus encoding the major cartilage collagen gene (COL2A1) was studied in a total of 19 cases of achondroplasia. No gross rearrangements were seen. The segregation of COL2A1 was examined in three affected kindreds using restriction site and length variants as genetic markers. In two kindreds discor...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.23.1.19
更新日期:1986-02-01 00:00:00
abstract:BACKGROUND:Following predictive testing for Huntington disease (HD), knowledge of one's carrier status may have consequences on disease onset. Our study aimed to address two questions. First, does knowledge of being a carrier of the pathological HD mutation trigger onset of the disease? Second, does this knowledge infl...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2016-104199
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:There are few empirical data to inform the debate surrounding the use and regulation of direct-to-consumer (DTC) genome-wide disease risk tests. This study aimed to determine the long term psychological, behavioural, and clinical impacts of genomic risk testing for common disease. METHODS:The Scripps Genomi...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2012-101207
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Enzyme deficiencies of the oxidative phosphorylation (OXPHOS) system may be caused by mutations in the mitochondrial DNA (mtDNA) or in the nuclear DNA. OBJECTIVE:To analyse the sequences of the mtDNA coding region in 25 patients with OXPHOS system deficiency to identify the underlying genetic defect. RESUL...
journal_title:Journal of medical genetics
pub_type: 信件
doi:10.1136/jmg.2006.042168
更新日期:2006-11-01 00:00:00
abstract::Cultivated cells obtained by amniocentesis for antenatal diagnosis were examined for the presence of keratin filaments by immunofluorescent staining techniques. In primary cultures, cells in fibroblast type colonies do not possess keratin filaments whereas cells in epithelial type colonies show positive staining of ke...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.19.6.433
更新日期:1982-12-01 00:00:00
abstract:BACKGROUND:The hallmark of the neurobehavioural phenotype of Williams-Beuren syndrome (WBS) is increased sociability and relatively preserved language skills, often described as opposite to autism spectrum disorders (ASD). However, the prevalence of ASD in WBS is 6-10 times higher than in the general population. We hav...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2019-106080
更新日期:2019-12-01 00:00:00
abstract::Patients affected with progressive myoclonus epilepsy of the Lafora type present during late adolescence with a characteristic EEG pattern and Lafora bodies seen on skin biopsy. The critical region for the Lafora gene has been localised to chromosome 6q24 flanked by the dinucleotide repeat markers D6S292 and D6S420. T...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.7.590
更新日期:1997-07-01 00:00:00
abstract::Mitochondria play a central role in the secretion of insulin by pancreatic beta-cells, and pathogenic mutations of mitochondrial DNA (mtDNA) can cause diabetes. The aetiology of type 2 diabetes has a strong genetic component, raising the possibility that genetic variants of mtDNA alter the risk of developing the disor...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2007.048876
更新日期:2007-06-01 00:00:00