Abstract:
:We report on two brothers and one maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia. The patients were born to normal and non-consanguineous parents. All other members of the family, almost exclusively females, were clinically normal, suggesting X linked inheritance. By multipoint linkage analysis with markers spanning the whole X chromosome, we have tentatively assigned the underlying genetic defect to Xp11.4-q21, achieving a maximum lod score of 1.3. This localisation overlaps MRXS3, a syndromic form of mental retardation resembling that found in the family described here, although with a milder presentation. We discuss the possibility that both phenotypes might be allelic variants of the same gene localised in the pericentromeric region of the X chromosome. Analysis of the X inactivation pattern in one potential and three obligate carrier females showed non-random inactivation of the allele linked to the disease. This finding may be interpreted as: (1) a negative selection effect on cells bearing the mutation on the active X chromosome; (2) both the disease causing gene and the X inactivation centre are simultaneously affected by the same alteration, a deletion for instance; or (3) the skewed inactivation is the consequence of an independent event randomly associated with the disease. In any case, the observation of consistent X inactivation supports X linkage of the disease.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Martínez F,Tomás M,Millán JM,Fernández A,Palau F,Prieto Fdoi
10.1136/jmg.35.4.284subject
Has Abstractpub_date
1998-04-01 00:00:00pages
284-7issue
4eissn
0022-2593issn
1468-6244journal_volume
35pub_type
杂志文章abstract::Neurofibromatosis type 1 is one of the most common inherited disorders with an incidence of 1 in 3000. The search for NF1 mutations has been hampered by the overall size of the gene, the large number of exons, and the high mutation rate. To date, fewer than 90 mutations have been reported to the NF1 mutation analysis ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.32.9.706
更新日期:1995-09-01 00:00:00
abstract::X linked hypohidrotic ectodermal dysplasia (XHED) affects many epithelial functions, including sweat gland formation. Female carriers who manifest XHED may have defective dentition or a patchy distribution of sweating or both, as determined by starch and iodine sweat testing. Such sweat testing can be useful in assign...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.28.5.330
更新日期:1991-05-01 00:00:00
abstract::Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A-->G is the most prevalent in all populations tested so far. Recently, th...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2006.042440
更新日期:2006-11-01 00:00:00
abstract::A 2-year-old boy with mental and growth retardation is presented; he has a 46,XY,r(10)(p15q26) chromosome complement. Five previously reported cases of ring chromosome 10 were reviewed and compared with the present case in an attempt to delineate a clinical syndrome. Since the first description, identified by Giemsa b...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.20.2.142
更新日期:1983-04-01 00:00:00
abstract:BACKGROUND:Somatic mutations are a major driver of cancer development and many have now been identified in various cancer types, but the comprehensive somatic mutation status of the normal tissues matched to tumours has not been revealed. METHOD:We analysed the somatic mutations of whole exome sequencing data in 392 p...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2020-106905
更新日期:2020-07-27 00:00:00
abstract::A child with ambiguous genitalia, brought up phenotypically male, had a 46,XX/46,XY karyotype. At laparotomy, he had a left sided ovary and uterus, and a right sided scrotal testis. The 46,XX line made up 50% of cells in the blood and 90% of cells in a skin biopsy. There were no cytogenetic polymorphisms. Analysis of ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.31.10.816
更新日期:1994-10-01 00:00:00
abstract::Angelman syndrome (AS) and Prader-Willi syndrome (PWS) have become the classical examples of genomic imprinting in man, as completely different phenotypes are generated by the absence of maternal (AS) or paternal (PWS) contributions to the q11-13 region of chromosome 15 as a result of deletion or uniparental disomy. A...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.29.12.853
更新日期:1992-12-01 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:BACKGROUND:Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control th...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2016-103956
更新日期:2017-01-01 00:00:00
abstract::Bazex-Dupre-Christol syndrome (BDCS) is an X linked dominant disorder of the hair follicle characterised by follicular atrophoderma, multiple basal cell carcinomas, hypotrichosis, milia, and localised hypohidrosis. Follicular atrophoderma (FA) are follicular funnel shaped depressions, "ice pick marks", seen most commo...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.33.6.493
更新日期:1996-06-01 00:00:00
abstract::A family of male limited gonadotrophin independent precocious puberty was examined for activating mutation of the LH receptor. A transition of A to G in nucleotide 1733 of the human LH receptor gene was identified in all affected males and in an unaffected carrier female. The mutation was shown by identifying a new re...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.32.7.553
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND:Four genetic causes of isolated congenital central hypothyroidism (CeH) have been identified, but many cases remain unexplained. We hypothesised the existence of other genetic causes of CeH with a Mendelian inheritance pattern. METHODS:We performed exome sequencing in two families with unexplained isolated ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2017-105113
更新日期:2018-10-01 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::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::DNA from 20 Italian haemophilia B patients was analysed by the Southern blotting technique and hybridisation to a factor IX cDNA probe. A large deletion of factor IX gene was detected in one patient with antibodies to the infused factor; the EcoRI pattern of the other 19 subjects examined was normal. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.22.4.305
更新日期:1985-08-01 00:00:00
abstract::A case of a supernumerary metacentric small chromosome, diagnosed at birth, is described. The cytogenetic findings support its identification as i(18p). The clinical development from birth to 12 months is reported, with particular attention given to the psychomotor retardation and to the immunological aspect. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.16.1.69
更新日期:1979-02-01 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::Recent studies have shown that the G-allele of MDM2 SNP309 (T/G) in the p53 tumour suppressor pathway can accelerate tumorigenesis and alter the risk of various cancers in women and not in men. In this report, data are presented from two independent groups of patients that suggest that the G-allele of SNP309 accelerat...
journal_title:Journal of medical genetics
pub_type: 信件
doi:10.1136/jmg.2006.043539
更新日期:2006-12-01 00:00:00
abstract::In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the af...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.1.23
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND/AIMS:The development of colorectal cancer and a variable range of extracolonic manifestations in familial adenomatous polyposis (FAP) is the result of the dominant inheritance of adenomatous polyposis coli (APC) gene mutations. In this study, direct mutation analysis of the APC gene was performed to determin...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::The risk of breast cancer for unaffected men who test positive for a BRCA2 mutation is based on very few retrospective studies. We have used both retrospective and prospective analysis in 321 families with pathogenic BRCA2 mutations. Three breast cancers occurred in male first-degree relatives after family ascertainme...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2009.075176
更新日期:2010-10-01 00:00:00
abstract::Shortening of the tubular bones of the hands and feet with cone shaped epiphyses is known as peripheral dysostosis and is common to several syndromes including acrodysostosis and Albright's hereditary osteodystrophy (AHO). The underlying defect in AHO is known to be a reduction in bioactivity of the alpha subunit of t...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.2.133
更新日期:1997-02-01 00:00:00
abstract:BACKGROUND:Tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1) and there is wide clinical variability of the tibial dysplasia in NF1, suggesting the possibility of genetic modifiers. Double inactivation of NF1 is postulated to be necessary for the development of tibial pseudarthrosis, but tissue or ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2014-102815
更新日期:2015-04-01 00:00:00
abstract::A female child with multiple vertebral and rib abnormalities is described. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.21.1.68
更新日期:1984-02-01 00:00:00
abstract:BACKGROUND:The clinical phenotypes of females with fragile X full mutations vary drastically. Comparisons of discordant monozygotic twins provide opportunities to ascertain crucial factors that influence disease phenotype penetrance. OBJECTIVE:To identify crucial factors influencing the phenotypic expression of fragil...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2013-101978
更新日期:2014-03-01 00:00:00
abstract::Two patients with partial monosomy of the short arm of chromosome 8 are described. Their clinical features were very similar. Comparison with previously reported patients confirms the existence of an 8p- syndrome. The importance of cytogenetic investigations in all infants with major congenital heart defect and facial...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.23.2.153
更新日期:1986-04-01 00:00:00
abstract::In this paper the costs and benefits associated with DNA diagnosis of subjects who are at risk of having a child with a monogenic disease and who seek genetic counselling because of their reproductive plans are predicted under various assumptions using a mathematical model. Four monogenic diseases have been considered...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.9.741
更新日期:1997-09-01 00:00:00
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, acc...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2018-105872
更新日期:2019-06-01 00:00:00
abstract::A family with an insertional type of chromosome rearrangement involving chromosomes 7 and 13 is reported. An interstitial deletion of a segment of chromosome 7 (7q32 leads to 34) had been inserted into the long arm of chromosome 13 at breakpoint q32. Segregation of this chromosome rearrangement gave rise to three subj...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.16.6.461
更新日期:1979-12-01 00:00:00
abstract:BACKGROUND:Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding cartilage associated protein. These proteins constitute together with cyclophilin B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2008.062729
更新日期:2009-04-01 00:00:00