MicroRNA-4516-mediated regulation of MAPK10 relies on 3' UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease.


BACKGROUND:Hirschsprung disease (HSCR) is a life-threatening congenital disorder in which the enteric nervous system is completely missing from the distal gut. Recent studies have shown that miR-4516 markedly inhibits cell migration, and as one of its potential targets, MAPK10 functions as a modifier for developing HSCR. We thus aimed to evaluate the role of miR-4516 and MAPK10 in HSCR and how they contribute to the pathogenesis of HSCR. METHODS:We examined 13 genetic variants using the MassArray system in a case-control study (n=1015). We further investigated miR-4516-mediated regulation of MAPK10 in HSCR cases and human neural cells, the effects of cis-acting elements in MAPK10 on miR-4516-mediated modulation and cell migration process. RESULTS:Three positive 3' UTR variants in MAPK10 were associated with altered HSCR susceptibility. We also showed that miR-4516 directly regulates MAPK10 expression, and this regulatory mechanism is significantly affected by the 3' UTR cis-acting elements of MAPK10. In addition, knock-down of MAPK10 rescued the effect of miR-4516 on the migration of human neural cells. CONCLUSION:Our findings indicate a key role of miR-4516 and its direct target MAPK10 in HSCR risk, and highlight the general importance of cis- and posttranscriptional modulation for HSCR pathogenesis.


J Med Genet


Wang Y,Jiang Q,Chakravarti A,Cai H,Xu Z,Wu W,Gu B,Li L,Cai W




Has Abstract


2020-09-01 00:00:00














  • Further observations on the Birmingham chimaera.

    abstract::The appropriate ABH-gene specified glycosyltransferases in the plasma of the Birmingham chimaera were estimated. These observatiions and the demonstration of A1Leb blood group specific glycosphingolipid in the plasma indicate that the minority population of red blood cells probably represents the true blood groups of ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Bird GW,Battey DA,Greenwell P,Mortimer CW,Watkins WM,Wingham J

    更新日期:1976-02-01 00:00:00

  • Echinocytes in families with Duchenne muscular dystrophy.

    abstract::The results of the present investigation have failed to confirm the suggestion that there is a significant increase in the proportion of echinocytes in preparation of fresh erythrocytes in patients with Duchenne muscular dystrophy and heterozygous carriers of this disorder. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Soltan HC

    更新日期:1977-08-01 00:00:00

  • Early infantile epileptic encephalopathy associated with a high voltage gated calcium channelopathy.

    abstract:BACKGROUND:Early infantile epileptic encephalopathies usually manifest as severely impaired cognitive and motor development and often result in a devastating permanent global developmental delay and intellectual disability. A large set of genes has been implicated in the aetiology of this heterogeneous group of disorde...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Edvardson S,Oz S,Abulhijaa FA,Taher FB,Shaag A,Zenvirt S,Dascal N,Elpeleg O

    更新日期:2013-02-01 00:00:00

  • Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes.

    abstract:BACKGROUND:Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal recessive mode of inheritance and consists of at least three subtypes. FHL2 subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while FHL with MUNC13-4 mutation was recently identified and designated as FHL3 subtype. OB...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Yamamoto K,Ishii E,Sako M,Ohga S,Furuno K,Suzuki N,Ueda I,Imayoshi M,Yamamoto S,Morimoto A,Takada H,Hara T,Imashuku S,Sasazuki T,Yasukawa M

    更新日期:2004-10-01 00:00:00

  • Lynch syndrome caused by MLH1 mutations is associated with an increased risk of breast cancer: a cohort study.

    abstract:INTRODUCTION:Lynch syndrome is known to cause an increased risk of malignancies, including bowel and endometrial cancers. However, the risk of breast cancer associated with mutations in the mismatch repair (MMR) genes that cause Lynch syndrome is still unclear. MATERIALS AND METHODS:This study assesses the cumulative ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Harkness EF,Barrow E,Newton K,Green K,Clancy T,Lalloo F,Hill J,Evans DG

    更新日期:2015-08-01 00:00:00

  • Fryns syndrome phenotype caused by chromosome microdeletions at 15q26.2 and 8p23.1.

    abstract:BACKGROUND:Fryns syndrome (FS) is the commonest autosomal recessive syndrome in which congenital diaphragmatic hernia (CDH) is a cardinal feature. It has been estimated that 10% of patients with CDH have FS. The autosomal recessive inheritance in FS contrasts with the sporadic inheritance for the majority of patients w...

    journal_title:Journal of medical genetics

    pub_type: 信件


    authors: Slavotinek A,Lee SS,Davis R,Shrit A,Leppig KA,Rhim J,Jasnosz K,Albertson D,Pinkel D

    更新日期:2005-09-01 00:00:00

  • Molecular analysis of late onset Huntington's disease.

    abstract::Late onset Huntington's disease is characterised by onset of symptoms after the age of 50 and is usually associated with a milder course. We have analysed the CAG trinucleotide repeat within the HD gene in 133 late onset patients from 107 extended families. The median upper allele size for the CAG repeat was 42 with a...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Kremer B,Squitieri F,Telenius H,Andrew SE,Theilmann J,Spence N,Goldberg YP,Hayden MR

    更新日期:1993-12-01 00:00:00

  • Family in which Duchenne's muscular dystrophy and protan colour blindness are segregating.

    abstract::A family is recorded in which Duchenne's muscular dystrophy and protan colour blindness are segregating. Of 4 members of the second generation at least one is a recombinant. The lod scores have been calculated and added to those already published. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Greig DN

    更新日期:1977-04-01 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

  • Three sisters with gonadoblastoma.

    abstract::Three sisters with gonadoblastoma and an 46,XY karyotype are presented. This observation suggests that heredity may play an important role in the genesis of the tumour. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Ionescu B,Maximilian C

    更新日期:1977-06-01 00:00:00

  • Studies of genetic linkage between adult polycystic kidney disease and three markers on chromosome 16.

    abstract::Adult polycystic kidney disease (APKD) is a common genetic disorder that is inherited as an autosomal dominant trait. Recent reports show that, in some families, the APKD gene shows close genetic linkage to two chromosome 16 specific genetic markers. We have been conducting a genetic linkage study using 29 polymorphic...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Watson ML,Wright AF,Macnicol AM,Allan PL,Clayton JF,Dempster M,Jeremiah SJ,Corney G,Hopkinson DA

    更新日期:1987-08-01 00:00:00

  • Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group.

    abstract::Genetic testing for hereditary cancer predisposition has evolved rapidly in recent years with the discovery of new genes, but there is much debate over the clinical utility of testing genes for which there are currently limited data regarding the degree of associated cancer risk. To address the discrepancies that have...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Taylor A,Brady AF,Frayling IM,Hanson H,Tischkowitz M,Turnbull C,Side L,UK Cancer Genetics Group (UK-CGG).

    更新日期:2018-06-01 00:00:00

  • Detection of maternal cell contamination in amniotic fluid cell cultures using fluorescent labelled microsatellites.

    abstract::A rapid PCR based assay was used to ascertain the presence of maternal cell contamination (MCC) in amniotic fluid cell cultures and to exclude MCC in cases where cytogenetic analysis was possible only from one primary cell culture. Six 6-carboxyfluorescein (FAM) and three 6-carboxyfluorescein hexachloride (HEX) labell...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Smith GW,Graham CA,Nevin J,Nevin NC

    更新日期:1995-01-01 00:00:00

  • Diagnostic issues in a family with late onset type 2 neurofibromatosis.

    abstract::We report a family with type 2 neurofibromatosis and late onset tumours. Five members of this family have developed hearing loss late in life, two of whom have only been shown to have the diagnosis in their seventies, and three other obligate gene carriers died undiagnosed at 64, 72, and 78 years of age. A missense mu...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Evans DG,Bourn D,Wallace A,Ramsden RT,Mitchell JD,Strachan T

    更新日期:1995-06-01 00:00:00

  • Trends in pyloric stenosis incidence, Atlanta, 1968 to 1982.

    abstract::Four studies reported an increasing incidence of pyloric stenosis during the late 1970s from geographically diverse areas of the United Kingdom. It was suggested that the increased incidence might be related to changes in infant feeding practices. We used data from the Metropolitan Atlanta Congenital Defects Program, ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Lammer EJ,Edmonds LD

    更新日期:1987-08-01 00:00:00

  • Parental origin of the X chromosome in a patient with a Robertsonian translocation and Turner's syndrome.

    abstract::We report on a proband with both a Robertsonian translocation and Turner's syndrome. Study of the parental origin of the X chromosome performed by microsatellite analysis indicates paternal origin of the X chromosome (Xpat). The occurrence of chromosome aberrations as a consequence of interchromosomal interactions is ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Krajinovic M,Ivanovic K,Mestroni L,Diklic V,Nikolis J

    更新日期:1994-03-01 00:00:00

  • The estimation of recurrence risks in monogenic disorders using flanking marker loci.

    abstract::A method is presented of calculating recurrence risks at a disease locus where there is information from flanking marker loci. This method uses output from the computer programme LIPED. Information from carrier detection tests and mutation at the disease locus can be taken into account in certain pedigrees. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Winter RM

    更新日期:1985-02-01 00:00:00

  • Molecular mechanisms of phenotypic variability in junctional epidermolysis bullosa.

    abstract:BACKGROUND:Junctional epidermolysis bullosa (JEB), a group of hereditary skin fragility disorders, is associated with a wide variety of phenotypes, although all forms are characterised by trauma induced skin blistering and tissue separation at the dermal-epidermal junction zone. A subgroup, coined JEB-other, is associa...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Kiritsi D,Kern JS,Schumann H,Kohlhase J,Has C,Bruckner-Tuderman L

    更新日期:2011-07-01 00:00:00

  • Genetic mapping of X linked ocular albinism: linkage analysis in British families.

    abstract::Genetic linkage studies were performed in 16 British families affected by X linked ocular albinism (XLOA) using RFLPs from the Xp22.3 region. Linkage was confirmed between the XLOA locus (OA1) and the loci DXS143 (dic56; Zmax = 15.90 at theta = 0.0, confidence interval (CI) 0-0.035), DXS85 (782; Zmax = 15.67 at theta ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Charles SJ,Moore AT,Yates JR

    更新日期:1992-08-01 00:00:00

  • Genotype-phenotype correlation in von Hippel-Lindau disease: identification of a mutation associated with VHL type 2A.

    abstract::A family with von Hippel-Lindau disease (VHL) type 2A has been shown to have a T to C missense mutation at nucleotide 547 of the VHL gene. This gives further support for the proposal to associate the 547 T to C mutation with phenotype VHL 2A. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Chen F,Slife L,Kishida T,Mulvihill J,Tisherman SE,Zbar B

    更新日期:1996-08-01 00:00:00

  • Hereditary haemorrhagic telangiectasia: a clinical analysis.

    abstract::Data from 98 patients with hereditary haemorrhagic telangiectasia (HHT) are presented. All were symptomatic by 40 years of age and 62% by 16 years. Nose bleeding was the first symptom of disease in 90% of cases with mucocutaneous telangiectases appearing 5 to 20 years later. Complications of HHT are discussed and an a...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Porteous ME,Burn J,Proctor SJ

    更新日期:1992-08-01 00:00:00

  • Unilateral radial aplasia and trisomy 22 mosaicism.

    abstract::A child with unilateral radial aplasia, asymmetry, other malformations, and severe physical and mental retardation is reported. In blood and bone marrow cultures a low mosaicism for trisomy 22 was found. In a few cells a chromosome 22 was missing. The importance of early cytogenetic analysis on large numbers of cells ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Dulitzky F,Shabtal F,Zlotogora J,Halbrecht I,Elian E

    更新日期:1981-12-01 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

  • De novo interstitial deletion del(1)(p21p32).

    abstract::A girl aged 14 years 9 months, overweight, with severe psychomotor retardation, short stature, a sheep-like face, malformed ears, skeletal and dermatoglyphic abnormalities, and partial deletion of the short arm of chromosome 1 is presented. The karyotype was 46,XX,del(1)(qter to p22::p32 to pter). ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Bene M,Duca-Marinescu A,Ioan D,Maximilian C

    更新日期:1979-08-01 00:00:00

  • A fertile male with cystic fibrosis: molecular genetic analysis.

    abstract::A family study is presented in which the father of a girl with severe cystic fibrosis (CF) was also found to have CF but was mildly affected. He was diagnosed with three positive sweat tests including one after suppression with fludrocortisone. Genetic analysis showed that he is a compound heterozygote with the delta ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Barreto C,Pinto LM,Duarte A,Lavinha J,Ramsay M

    更新日期:1991-06-01 00:00:00

  • A large multisite cancer family is linked to BRCA2.

    abstract::We identified a large French-Canadian family with 21 cases of breast cancer, including two affected brothers. Segregation of markers from chromosome 13q in this family showed linkage to the BRCA2 gene locus (lod = 3.67 at D13S289). A number of cancers of other types occurred in this family, including three cases of pr...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Tonin P,Ghadirian P,Phelan C,Lenoir GM,Lynch HT,Letendre F,Belanger D,Monté M,Narod SA

    更新日期:1995-12-01 00:00:00

  • Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.

    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 ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Martínez F,Tomás M,Millán JM,Fernández A,Palau F,Prieto F

    更新日期:1998-04-01 00:00:00

  • HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.

    abstract:BACKGROUND:Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. METHODS:Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: five HPT-JT, three FIH...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Howell VM,Haven CJ,Kahnoski K,Khoo SK,Petillo D,Chen J,Fleuren GJ,Robinson BG,Delbridge LW,Philips J,Nelson AE,Krause U,Hammje K,Dralle H,Hoang-Vu C,Gimm O,Marsh DJ,Morreau H,Teh BT

    更新日期:2003-09-01 00:00:00

  • Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation.

    abstract:BACKGROUND:Infantile-onset encephalopathy and hypertrophic cardiomyopathy caused by mitochondrial oxidative phosphorylation defects are genetically heterogeneous with defects involving both the mitochondrial and nuclear genomes. OBJECTIVE:To identify the causative genetic defect in two sisters presenting with lethal i...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Spiegel R,Saada A,Flannery PJ,Burté F,Soiferman D,Khayat M,Eisner V,Vladovski E,Taylor RW,Bindoff LA,Shaag A,Mandel H,Schuler-Furman O,Shalev SA,Elpeleg O,Yu-Wai-Man P

    更新日期:2016-02-01 00:00:00

  • Duchenne muscular dystrophy: negative electroretinograms and normal dark adaptation. Reappraisal of assignment of X linked incomplete congenital stationary night blindness.

    abstract::Aland Island eye disease (AIED) and X linked congenital stationary night blindness (CSNB) have been mapped to Xp11.3. Patients have been described with deletions of the Duchenne muscular dystrophy (DMD) gene who also had a negative electroretinogram (ERG) similar to that seen in patients with CSNB and AIED. This seems...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Jensen H,Warburg M,Sjö O,Schwartz M

    更新日期:1995-05-01 00:00:00