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 agenesis and is radiographically closely related to SRP type IV (Beemer-Langer; MIM 269860) which is distinguished by bowed radii and ulnae and relatively well tubulated tibiae. NEK1 mutations have been recently identified in SRP type II. Double heterozygosity for mutations in both NEK1 and DYNC2H1 in one SRP type II case supported possible digenic diallelic inheritance. METHODS:The aim of this study was to screen DYNC2H1 and NEK1 in 13 SRP type II cases and seven SRP type IV cases. It was not possible to screen DYNC2H1 in two patients due to insufficient amount of DNA. RESULTS:The study identified homozygous NEK1 mutations in 5/13 SRP type II and compound heterozygous DYNC2H1 mutations in 4/12 cases. Finally, NEK1 and DYNC2H1 were excluded in 3/12 SRP type II and in all SRP type IV cases. The main difference between the mutation positive SRP type II group and the mutation negative SRP type II group was the presence of holoprosencephaly and polymycrogyria in the mutation negative group. CONCLUSION:This study confirms that NEK1 is one gene causing SRP type II but also reports mutations in DYNC2H1, expanding the phenotypic spectrum of DYNC2H1 mutations. The exclusion of NEK1 and DYNC2H1 in 3/12 SRP type II and in all SRP type IV cases further support genetic heterogeneity.

journal_name

J Med Genet

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

doi

10.1136/jmedgenet-2011-100717

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

227-33

issue

4

eissn

0022-2593

issn

1468-6244

pii

jmedgenet-2011-100717

journal_volume

49

pub_type

杂志文章
  • Carrier risk status changes resulting from mutation testing in hereditary non-polyposis colorectal cancer and hereditary breast-ovarian cancer.

    abstract:CONTEXT:In hereditary cancer syndrome families with an identified cancer associated mutation, mutation testing changes the carrier risk status of the tested person and may change the carrier risk status of relatives. OBJECTIVE:This study aimed to describe the change in the distribution of carrier risk status resulting...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,多中心研究

    doi:10.1136/jmg.40.8.591

    authors: Watson P,Narod SA,Fodde R,Wagner A,Lynch JF,Tinley ST,Snyder CL,Coronel SA,Riley B,Kinarsky Y,Lynch HT

    更新日期:2003-08-01 00:00:00

  • Fragile X syndrome is less common than previously estimated.

    abstract::In 1986, a population study of school children in the city of Coventry gave an overall prevalence in males and females for fragile X syndrome of 1/952. The 29 children diagnosed as having fragile X syndrome in this study have been re-evaluated with molecular diagnostic techniques. Eighteen of the original 29 children ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.34.1.1

    authors: Morton JE,Bundey S,Webb TP,MacDonald F,Rindl PM,Bullock S

    更新日期:1997-01-01 00:00:00

  • Pericentric inversion of chromosome 7 (inv(7) (p22q11.2)) and ring chromosome 8 (r(8) (p23q24.3)) in a girl with minor anomalies.

    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

    authors: Verma RS,Conte RA,Pitter JH,Luke S

    更新日期:1992-01-01 00:00:00

  • De novo ring chromosome 3: a new case with a mild phenotype.

    abstract::We report an 18 year old female with a de novo ring chromosome 3 found after investigation for short stature. Her karyotype was interpreted as 46,XX, r(3)(p26.2q29). Her phenotype is milder than previously reported cases and illustrates the mild end of the spectrum of the ring chromosome 3 phenotype. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.28.8.536

    authors: McKinley M,Colley A,Sinclair P,Donnai D,Andrews T

    更新日期:1991-08-01 00:00:00

  • Attitudes towards predictive testing in Huntington's disease: a recent survey in Belgium.

    abstract::After the publication of evidence of the existence of a DNA polymorphism closely linked to the gene for Huntington's disease, attitudes towards predictive testing for Huntington's disease were evaluated in Belgium in a group of persons who are at risk for the disease and in a smaller group of their partners. The perce...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.24.5.275

    authors: Evers-Kiebooms G,Cassiman JJ,van den Berghe H

    更新日期:1987-05-01 00:00:00

  • Porencephalic cyst in pycnodysostosis.

    abstract::We describe a case of pycnodysostosis with porencephaly and suggest an explanation for the porencephaly by a mechanism of imbalance between brain growth and its vascular supply and a normal but unopposed cerebrospinal fluid pressure. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.12.782

    authors: Figueiredo J,Reis A,Vaz R,Leáo M,Cruz C

    更新日期:1989-12-01 00:00:00

  • Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.

    abstract::A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR activity and associated with modestly increased plasma homocysteine concentrations. Since underlying maternal vascular disease increases the risk of pre-eclampsi...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.34.6.525

    authors: Sohda S,Arinami T,Hamada H,Yamada N,Hamaguchi H,Kubo T

    更新日期:1997-06-01 00:00:00

  • Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?

    abstract::The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the cra...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.37.1.26

    authors: Reardon W,Smith A,Honour JW,Hindmarsh P,Das D,Rumsby G,Nelson I,Malcolm S,Adès L,Sillence D,Kumar D,DeLozier-Blanchet C,McKee S,Kelly T,McKeehan WL,Baraitser M,Winter RM

    更新日期:2000-01-01 00:00:00

  • Atypical hereditary neuropathy with liability to pressure palsies (HNPP): the value of direct DNA diagnosis.

    abstract::We report two patients with suspected hereditary liability to pressure palsies. Neurophysiological studies showed a mixed axonal-demyelinating sensory-motor polyneuropathy with focal slowing of conduction velocities at the common sites of entrapment. Morphological studies on sural nerve biopsy from the proband showed ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.34.11.889

    authors: Sessa M,Nemni R,Quattrini A,Del Carro U,Wrabetz L,Canal N

    更新日期:1997-11-01 00:00:00

  • Cleidocranial dysplasia: clinical and molecular genetics.

    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:

    authors: Mundlos S

    更新日期:1999-03-01 00:00:00

  • Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment.

    abstract:OBJECTIVE:Deficiency of α-galactosidase A (αGal-A) in Fabry disease leads to the accumulation mainly of globotriaosylceramide (GL3) in multiple renal cell types. Glomerular podocytes are relatively resistant to clearance of GL3 inclusions by enzyme replacement therapy (ERT). Migalastat, an orally bioavailable small mol...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2017-104826

    authors: Mauer M,Sokolovskiy A,Barth JA,Castelli JP,Williams HN,Benjamin ER,Najafian B

    更新日期:2017-11-01 00:00:00

  • Benign muscular dystrophy: risk calculation in families with consanguinity.

    abstract::This report concerns two families in which the index patients are sporadic cases of a benign form of muscular dystrophy. In both families the sisters of the patients have married a close relative. The respective risks for a child of these consanguineous marriages being affected with either X linked Becker muscular dys...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.5.299

    authors: Wolff G,Müller CR,Grimm T

    更新日期:1989-05-01 00:00:00

  • Genetics of Parkinson's disease and related disorders.

    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

    authors: Zhang PL,Chen Y,Zhang CH,Wang YX,Fernandez-Funez P

    更新日期:2018-02-01 00:00:00

  • Direct molecular analysis of myotonic dystrophy in the German population: important considerations in genetic counselling.

    abstract::Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat at the DM locus on chromosome 19. Direct genomic analysis in the German population was carried out on 18 DM families, six families with equivocal diagnosis, 69 subjects with equivocal clinical diagnosis, and 100 co...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.32.8.645

    authors: Meiner A,Wolf C,Carey N,Okitsu A,Johnson K,Shelbourne P,Kunath B,Sauermann W,Thiele H,Kupferling P

    更新日期:1995-08-01 00:00:00

  • Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus.

    abstract:BACKGROUND:Intellectual disability (ID) is one of the most common forms of disability worldwide, displaying a wide range of aetiologies and affecting nearly 2% of the global population. OBJECTIVE:To describe a novel autosomal recessive form of ID with strabismus and its underlying aetiology. MATERIALS AND METHODS:Aut...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2012-101378

    authors: Alazami AM,Hijazi H,Al-Dosari MS,Shaheen R,Hashem A,Aldahmesh MA,Mohamed JY,Kentab A,Salih MA,Awaji A,Masoodi TA,Alkuraya FS

    更新日期:2013-07-01 00:00:00

  • Lead levels in human placentae from normal and malformed births.

    abstract::Placental lead levels were studied in a series of Birmingham births classified by stillbirth, neonatal death, or survival beyond one week. There was an appreciable range of lead levels even in normal births (0.15-3.56 microgram/g) but nevertheless average results showed a pronounced excess of lead in those who failed ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.14.5.339

    authors: Wibberley DG,Khera AK,Edwards JH,Rushton DI

    更新日期:1977-10-01 00:00:00

  • Retrospective natural history of thymidine kinase 2 deficiency.

    abstract:BACKGROUND:Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. OBJECTIVE:To perfor...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,多中心研究

    doi:10.1136/jmedgenet-2017-105012

    authors: Garone C,Taylor RW,Nascimento A,Poulton J,Fratter C,Domínguez-González C,Evans JC,Loos M,Isohanni P,Suomalainen A,Ram D,Hughes MI,McFarland R,Barca E,Lopez Gomez C,Jayawant S,Thomas ND,Manzur AY,Kleinsteuber K,Marti

    更新日期:2018-08-01 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

    doi:10.1136/jmedgenet-2019-106598

    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

  • BRCA1 and BRCA2 mutation analysis in 86 early onset breast/ovarian cancer patients.

    abstract::Eighty-six women fulfilling specific selection criteria were studied for germline mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2, using the protein truncation test (PTT). Nine germline mutations were identified, six in BRCA1 and three in BRCA2. Of the six BRCA1 mutations, three have previously be...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.34.12.990

    authors: Garvin AM,Attenhofer-Haner M,Scott RJ

    更新日期:1997-12-01 00:00:00

  • First trimester fetal diagnosis of genetic disorders: clinical evaluation of 250 cases.

    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

    authors: Brambati B,Simoni G,Danesino C,Oldrini A,Ferrazzi E,Romitti L,Terzoli G,Rossella F,Ferrari M,Fraccaro M

    更新日期:1985-04-01 00:00:00

  • Evidence based medicine in practice: lessons from a Scottish clinical genetics project.

    abstract:OBJECTIVE:To establish national clinical guidelines and integrated care pathways for five conditions (tuberous sclerosis (TS), Huntington's disease (HD), myotonic dystrophy (MD), neurofibromatosis type 1 (NF1), and Marfan syndrome (MS)) and audit their use in Scotland. DESIGN:Systematic review of published reports fol...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.37.9.684

    authors: Campbell H,Bradshaw N,Davidson R,Dean J,Goudie D,Holloway S,Porteous M

    更新日期:2000-09-01 00:00:00

  • Atypical serum cholinesterase in a family with congenital distichiasis.

    abstract::This paper describes the coexistence of genetically determined reduced cholinesterase activity and congenital distichiasis in the same family. The pedigree suggests that these two autosomal dominant diseases are segregated independently and do not show evidence of linkage. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.13.6.514

    authors: Shammas HF,Tabbara KF,der Kaloustian VM

    更新日期:1976-12-01 00:00:00

  • The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists.

    abstract:PURPOSE AND SCOPE:The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,实务指引

    doi:10.1136/jmedgenet-2015-103144

    authors: Boycott K,Hartley T,Adam S,Bernier F,Chong K,Fernandez BA,Friedman JM,Geraghty MT,Hume S,Knoppers BM,Laberge AM,Majewski J,Mendoza-Londono R,Meyn MS,Michaud JL,Nelson TN,Richer J,Sadikovic B,Skidmore DL,Stockley T,

    更新日期:2015-07-01 00:00:00

  • Sickle cell disease in Sicily.

    abstract::The chemical and physical properties of haemoglobin S derived from homozygotes for this haemoglobin in Sicily were examined, as well as some erythrocytic characteristics. Sicilian Hb S was identical to that found in USA black patients in electrophoretic mobility on both starch and citrate agar media, solubility, mecha...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.17.1.34

    authors: Roth EF Jr,Schiliro G,Russo A,Musumeci S,Rachmilewitz E,Neske V,Nagel R

    更新日期:1980-02-01 00:00:00

  • Duchenne muscular dystrophy in Wales: impact of DNA linkage analysis and cDNA deletion screening.

    abstract::A register of families with Duchenne muscular dystrophy (DMD) has been maintained in Wales since 1973. Since 1986 we have attempted to refine carrier status, and when necessary offer prenatal diagnosis, for those at significant risk by using intragenic probes. cDNA probes were included from the beginning of 1988. Thir...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.9.565

    authors: Norman AM,Upadhyaya M,Thomas NS,Roberts K,Harper PS

    更新日期:1989-09-01 00:00:00

  • The non-deletion alpha thalassaemia/mental retardation syndrome: further support for X linkage.

    abstract::It has previously been suggested that the non-deletion form of the alpha thalassaemia/mental retardation syndrome may be an X linked disorder. We describe four brothers with this syndrome in whom the diagnosis was first suspected because of their characteristic clinical features, although these varied somewhat from on...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.28.11.742

    authors: Donnai D,Clayton-Smith J,Gibbons RJ,Higgs DR

    更新日期:1991-11-01 00:00:00

  • Mutation screening in British 21-hydroxylase deficiency families and development of novel microsatellite based approaches to prenatal diagnosis.

    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 fr...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:

    authors: Lako M,Ramsden S,Campbell RD,Strachan T

    更新日期:1999-02-01 00:00:00

  • Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy.

    abstract:BACKGROUND:Hypertrophic cardiomyopathy (HCM) is frequently fatal in infancy. Mitochondrial disease causing infantile HCM is characterised by extreme biochemical and genetic heterogeneity, but deficiency of respiratory chain complex I is observed relatively frequently. Identification of the precise genetic basis has pro...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2011-100340

    authors: Fassone E,Taanman JW,Hargreaves IP,Sebire NJ,Cleary MA,Burch M,Rahman S

    更新日期:2011-10-01 00:00:00

  • Favism: looking for an autosomal gene associated with glucose-6-phosphate dehydrogenase deficiency.

    abstract::Favism is a severe, acute haemolytic anaemia which occurs in about 20% of G6PD deficient subjects after ingestion of fava beans. Since not all G6PD deficient subjects are sensitive to fava beans, the possibility has been suggested that extra erythrocytic factors may play an important role in the susceptibility to haem...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.21.4.278

    authors: Mareni C,Repetto L,Forteleoni G,Meloni T,Gaetani GF

    更新日期:1984-08-01 00:00:00

  • Genomic rearrangements of the GREM1-FMN1 locus cause oligosyndactyly, radio-ulnar synostosis, hearing loss, renal defects syndrome and Cenani--Lenz-like non-syndromic oligosyndactyly.

    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

    authors: Dimitrov BI,Voet T,De Smet L,Vermeesch JR,Devriendt K,Fryns JP,Debeer P

    更新日期:2010-08-01 00:00:00