Instability of the CGG repeat at the FRAXA locus and variable phenotypic expression in a large fragile X pedigree.


: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 cytogenetic and molecular status. We have studied, in a large fragile X family, the correlation between the molecular data and the phenotypic expression of the syndrome. We report two brothers who carry identical unmethylated premutated alleles but present different clinical phenotypes. We also suggest that reductions in allele size from one generation to another may be, as in other diseases, because of triplet amplifications, more common at the FRAXA locus than previously thought.


J Med Genet


Pintado E,de Diego Y,Hmadcha A,Carrasco M,Sierra J,Lucas M




Has Abstract


1995-11-01 00:00:00












  • Neuropsychological characteristics of Huntington's disease carriers: a double blind study.

    abstract::A cohort of 33 people at risk for Huntington's disease (HD), applying for genetic testing, were tested with a battery of neuropsychological tests covering attentional, visuospatial, learning, memory, and planning functions. A psychiatric rating scale, SCL-90R, was also applied, mainly as a control, since cognitive dys...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Rosenberg NK,Sørensen SA,Christensen AL

    更新日期:1995-08-01 00:00:00

  • Prenatal diagnosis of the common haemoglobin disorders.

    abstract::New techniques of DNA analysis have been applied to the prenatal diagnosis of the common haemoglobin disorders. Currently, it is possible to provide a comprehensive programme for the prevention of these conditions, although this entails the use of several different techniques including globin chain synthesis analysis,...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Weatherall DJ,Old JM,Thein SL,Wainscoat JS,Clegg JB

    更新日期:1985-12-01 00:00:00

  • Addition of pathology and biomarker information significantly improves the performance of the Manchester scoring system for BRCA1 and BRCA2 testing.

    abstract:BACKGROUND:Selection for genetic testing of BRCA1/BRCA2 is an important area of healthcare. Although testing costs for mutational analysis are falling, costs in North America remain in excess of US$3000 (UK price can be 690 pounds). Guidelines in most countries use a 10-20% threshold of detecting a mutation in BRCA1/2 ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Evans DG,Lalloo F,Cramer A,Jones EA,Knox F,Amir E,Howell A

    更新日期:2009-12-01 00:00:00

  • CCMG practice guideline: laboratory guidelines for next-generation sequencing.

    abstract::PurposeThe purpose of this document is to provide guidance for the use of next-generation sequencing (NGS, also known as massively parallel sequencing or MPS) in Canadian clinical genetic laboratories for detection of genetic variants in genomic DNA and mitochondrial DNA for inherited disorders, as well as somatic var...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Hume S,Nelson TN,Speevak M,McCready E,Agatep R,Feilotter H,Parboosingh J,Stavropoulos DJ,Taylor S,Stockley TL,Canadian College of Medical Geneticists (CCMG).

    更新日期:2019-12-01 00:00:00

  • Map of 16 polymorphic loci on the short arm of chromosome 16 close to the polycystic kidney disease gene (PKD1).

    abstract::To define the PKD1 locus further, the gene involved in the most frequent form of adult polycystic kidney disease, probes from 16 polymorphic loci were mapped on 16p13.1-pter with the combined use of cell lines containing rearranged chromosomes and family studies. Five breakpoints in the distal part of 16p arbitrarily ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Breuning MH,Snijdewint FG,Brunner H,Verwest A,Ijdo JW,Saris JJ,Dauwerse JG,Blonden L,Keith T,Callen DF

    更新日期:1990-10-01 00:00:00

  • Linkage analysis in Marfan syndrome.

    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


    authors: Schwartz RC,Blanton SH,Hyde CA,Sottile TR Jr,Hudgins L,Sarfarazi M,Tsipouras P

    更新日期:1990-02-01 00:00:00

  • "Compensatory" uniparental disomy of chromosome 21 in two cases.

    abstract::Two cases of growth failure, microcephaly, facial dysmorphism, muscular hypertonia, and severe psychomotor retardation are described. At birth, both cases had cytogenetic mosaicism in lymphocytes and skin fibroblasts, in case 1 ring chromosome 21 and monosomy 21 and in case 2, deletion of chromosome 21 and monosomy 21...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Bartsch O,Petersen MB,Stuhlmann I,Mau G,Frantzen M,Schwinger E,Antonarakis SE,Mikkelsen M

    更新日期:1994-07-01 00:00:00

  • Severe developmental delay and multiple strawberry naevi: a new syndrome?

    abstract::An 18 month old girl with dysmorphic features, severe developmental delay, multiple strawberry naevi, and capillary naevi is described. No previous report of a similar association of features has been identified. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Upton CJ,Young ID

    更新日期:1993-10-01 00:00:00

  • Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis.

    abstract:BACKGROUND:Infertility affects approximately 15% of couples worldwide with male infertility being responsible for approximately 50% of cases. Although accumulating evidence demonstrates the critical role of the X chromosome in spermatogenesis during the last few decades, the expression patterns and potential impact of ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Lu C,Zhang Y,Qin Y,Xu Q,Zhou R,Cui Y,Zhu Y,Zhang X,Zhang J,Wei X,Wang M,Hang B,Mao JH,Snijders AM,Liu M,Hu Z,Shen H,Zhou Z,Guo X,Wu X,Wang X,Xia Y

    更新日期:2021-01-01 00:00:00

  • Correlation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 in the APC gene.

    abstract::The APC gene was investigated in 31 unrelated polyposis coli families by SSCP analysis and the protein truncation test. Twenty-three germline mutations were identified which gave rise to a variety of different phenotypes. Some of these mutations have already been described; however we report six previously unpublished...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Dobbie Z,Spycher M,Mary JL,Häner M,Guldenschuh I,Hürliman R,Amman R,Roth J,Müller H,Scott RJ

    更新日期:1996-04-01 00:00:00

  • NEK1 and DYNC2H1 are both involved in short rib polydactyly Majewski type but not in Beemer Langer cases.

    abstract:BACKGROUND:The lethal short rib polydactyly syndromes (SRP type I-IV) are characterised by notably short ribs, short limbs, polydactyly, multiple anomalies of major organs, and autosomal recessive mode of inheritance. Among them, SRP type II (Majewski; MIM 263520) is characterised by short ovoid tibiae or tibial agenes...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: El Hokayem J,Huber C,Couvé A,Aziza J,Baujat G,Bouvier R,Cavalcanti DP,Collins FA,Cordier MP,Delezoide AL,Gonzales M,Johnson D,Le Merrer M,Levy-Mozziconacci A,Loget P,Martin-Coignard D,Martinovic J,Mortier GR,Perez MJ

    更新日期:2012-04-01 00:00:00

  • De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy.

    abstract:BACKGROUND:Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epile...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: de Lange IM,Helbig KL,Weckhuysen S,Møller RS,Velinov M,Dolzhanskaya N,Marsh E,Helbig I,Devinsky O,Tang S,Mefford HC,Myers CT,van Paesschen W,Striano P,van Gassen K,van Kempen M,de Kovel CG,Piard J,Minassian BA,Nezar

    更新日期:2016-12-01 00:00:00

  • Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 in the muscular dystrophies.

    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


    authors: Jones KJ,Kim SS,North KN

    更新日期:1998-05-01 00:00:00

  • Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family.

    abstract:BACKGROUND:Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor beta (TGF-beta) family which plays a key role in cell growth, have r...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Thomson JR,Machado RD,Pauciulo MW,Morgan NV,Humbert M,Elliott GC,Ward K,Yacoub M,Mikhail G,Rogers P,Newman J,Wheeler L,Higenbottam T,Gibbs JS,Egan J,Crozier A,Peacock A,Allcock R,Corris P,Loyd JE,Trembath RC,Nic

    更新日期:2000-10-01 00:00:00

  • Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways.

    abstract:BACKGROUND:The cohesin complex plays an essential role in genome organisation and cell division. A full complement of the cohesin complex and its regulators is important for normal development, since heterozygous mutations in genes encoding these components can be sufficient to produce a disease phenotype. The implicat...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Schierding W,Horsfield JA,O'Sullivan JM

    更新日期:2020-09-11 00:00:00

  • Hereditary costovertebral dysplasia with malignant cerebral tumour.

    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


    authors: David TJ,Glass A

    更新日期:1983-12-01 00:00:00

  • Impaired male sex development in an infant with molecularly defined partial 9p monosomy: implication for a testis forming gene(s) on 9p.

    abstract::This paper describes a genetically male infant with impaired male sex development and partial 9p monosomy. The external genitalia were ambiguous with microphallus (penile length at birth 10 mm, mean age matched normal length 29 mm (SD 5)), hypospadias, and hypoplastic scrotum. The tests were undescended and severely h...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Ogata T,Muroya K,Matsuo N,Hata J,Fukushima Y,Suzuki Y

    更新日期:1997-04-01 00:00:00

  • Prenatal diagnosis of genetic disorders.

    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


    authors: Niermeijer MF,Sachs ES,Jahodova M,Tichelaar-Klepper C,Kleijer WJ,Galjaard H

    更新日期:1976-06-01 00:00:00

  • Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy.

    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


    authors: Votruba M,Moore AT,Bhattacharya SS

    更新日期:1998-10-01 00:00:00

  • Partial deletions are associated with an increased risk of complete deletion in AZFc: a new insight into the role of partial AZFc deletions in male infertility.

    abstract:BACKGROUND:The AZFc region on the human Y chromosome has been found to be functionally important in spermatogenesis. Complete AZFc deletion is one of the most frequent causes of male infertility and the roles of partial AZFc deletions (gr/gr and b2/b3 deletions) in spermatogenesis are controversial. METHODS:To further...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Zhang F,Lu C,Li Z,Xie P,Xia Y,Zhu X,Wu B,Cai X,Wang X,Qian J,Wang X,Jin L

    更新日期:2007-07-01 00:00:00

  • Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency.

    abstract:BACKGROUND:Isolated cytochrome c oxidase (COX) deficiency is usually associated with mutations in several factors involved in the biogenesis of COX. METHODS:We describe a patient with atypical, long surviving Leigh syndrome carrying two novel mutations in the COX15 gene, which encodes an enzyme involved in the biosynt...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Bugiani M,Tiranti V,Farina L,Uziel G,Zeviani M

    更新日期:2005-05-01 00:00:00

  • Parkinson's disease GWAS-linked Park16 carriers show greater motor progression.

    abstract:BACKGROUND:Data on the long-term motor outcomes of genome-wide association study (GWAS)-linked Parkinson disease (PD) carriers are useful for clinical management. OBJECTIVES:To characterise the association between GWAS-linked PARK16 gene variant and disease progression in PD over a 9-year time frame. METHODS:Over a 9...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Deng X,Xiao B,Allen JC,Ng E,Foo JN,Lo YL,Tan LCS,Tan EK

    更新日期:2019-11-01 00:00:00

  • Extra small metacentric chromosome identified as i(18p).

    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


    authors: Rocchi M,Stormi M,Archidiacono N,Filippi G

    更新日期:1979-02-01 00:00:00

  • Fragile X syndrome with FMR1 and FMR2 deletion.

    abstract::We report a 13 year old boy with fragile X syndrome resulting from a de novo deletion of the FMR1 and FMR2 genes extending from (and including) DXS7536 proximally to FMR2 distally. The patient has severe developmental delay, epilepsy, and behavioural difficulties, including autistic features. He has epicanthic folds, ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Moore SJ,Strain L,Cole GF,Miedzybrodzka Z,Kelly KF,Dean JC

    更新日期:1999-07-01 00:00:00

  • Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy.

    abstract:BACKGROUND:Ethylmalonic encephalopathy (EE) is a rare autosomal recessive metabolic disorder characterised by progressive encephalopathy, recurrent petechiae, acrocyanosis and chronic diarrhoea, with a fatal outcome in early in life. METHODS:14 patients with EE were investigated for mutations in the ETHE1 gene. RESUL...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Mineri R,Rimoldi M,Burlina AB,Koskull S,Perletti C,Heese B,von Döbeln U,Mereghetti P,Di Meo I,Invernizzi F,Zeviani M,Uziel G,Tiranti V

    更新日期:2008-07-01 00:00:00

  • Intermediate C9orf72 alleles in neurological disorders: does size really matter?

    abstract::C9orf72 repeat expansions is a major cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Sizes of <20 hexanucleotide repeats are observed in controls, while up to thousands associate with disease. Intermediate C9orf72 repeat lengths, however, remain uncertain. We systemat...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Ng ASL,Tan EK

    更新日期:2017-09-01 00:00:00

  • Mutations in IRS4 are associated with central hypothyroidism.

    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


    authors: Heinen CA,de Vries EM,Alders M,Bikker H,Zwaveling-Soonawala N,van den Akker ELT,Bakker B,Hoorweg-Nijman G,Roelfsema F,Hennekam RC,Boelen A,van Trotsenburg ASP,Fliers E

    更新日期:2018-10-01 00:00:00

  • Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers.

    abstract::Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucocilia...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Bonneau D,Raymond F,Kremer C,Klossek JM,Kaplan J,Patte F

    更新日期:1993-03-01 00:00:00

  • Episodic ataxia and hemiplegia caused by the 8993T->C mitochondrial DNA mutation.

    abstract::The m.8993T-->C MTATP6 mutation of mitochondrial DNA (mtDNA) usually causes mitochondrial disease in childhood, but was recently described in a family with adult onset ataxia and polyneuropathy. Cytochrome c oxidase muscle histochemistry, which is the standard clinical investigation for mitochondrial disease in adults...

    journal_title:Journal of medical genetics

    pub_type: 信件


    authors: Craig K,Elliott HR,Keers SM,Lambert C,Pyle A,Graves TD,Woodward C,Sweeney MG,Davis MB,Hanna MG,Chinnery PF

    更新日期:2007-12-01 00:00:00

  • De novo t(X;21)(q28;q11) in a girl with phenotypic features of Williams-Beuren syndrome.

    abstract::We describe a female infant with mental retardation and some of the phenotypic features of Williams-Beuren syndrome. Chromosome analysis showed t(X;21)(q28;q11). Diagnosis, inactivation of the X chromosome, and possible involvement of the translocation breakpoints in the pathogenesis of this syndrome are discussed. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Telvi L,Pinard JM,Ion R,Sinet PM,Nicole A,Feingold J,Dulac O,Pompidou A,Ponsot G

    更新日期:1992-10-01 00:00:00