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














  • 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

  • Genotype-phenotype correlation in hereditary multiple exostoses.

    abstract::Hereditary multiple exostoses (HME) is a genetically heterogeneous autosomal dominant disorder characterised by the development of bony protuberances mainly located on the long bones. Three HME loci have been mapped to chromosomes 8q24 (EXT1), 11p11-13 (EXT2), and 19p (EXT3). The EXT1 and EXT2 genes encode glycosyltra...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Francannet C,Cohen-Tanugi A,Le Merrer M,Munnich A,Bonaventure J,Legeai-Mallet L

    更新日期:2001-07-01 00:00:00

  • Severe intrauterine growth retardation, blepharophimosis, and cylindrical nose with midline groove: a new syndrome?

    abstract::A malformed female infant is described. In addition to cardiac, renal, and skeletal (rib) anomalies, severe intrauterine growth retardation and distinct facial dysmorphism were present. The question is raised whether this child represents a new syndrome. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: de Die-Smulders CE,Droog RP,van Dijk M,Fryns JP

    更新日期:1993-06-01 00:00:00

  • Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB.

    abstract:BACKGROUND:Disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signalling causes pulmonary alveolar proteinosis (PAP). Rarely, genetic defects in neonatal or infant-onset PAP have been identified in CSF2RA. However, no report has clearly identified any function-associated genetic defect in CSF2RB. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Tanaka T,Motoi N,Tsuchihashi Y,Tazawa R,Kaneko C,Nei T,Yamamoto T,Hayashi T,Tagawa T,Nagayasu T,Kuribayashi F,Ariyoshi K,Nakata K,Morimoto K

    更新日期:2011-03-01 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


    authors: Wolff G,Müller CR,Grimm T

    更新日期:1989-05-01 00:00:00

  • Mutations in the TSC1 gene account for a minority of patients with tuberous sclerosis.

    abstract::Tuberous sclerosis (TSC) is an autosomal dominant disorder characterised by tumour-like malformations (hamartomas) of the brain, skin, and other organs, often associated with seizures and learning disability. There is genetic heterogeneity with loci for TSC on chromosomes 9q34 (TSC1) and 16p13.3 (TSC2). The recently c...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Ali JB,Sepp T,Ward S,Green AJ,Yates JR

    更新日期:1998-12-01 00:00:00

  • Maternal age specific risk rate estimates for Down syndrome among live births in whites and other races from Ohio and metropolitan Atlanta, 1970-1989.

    abstract::Our primary objective was to estimate, by one year and five year intervals, maternal age specific risk rates for Down syndrome among whites and among other races from two different populations, metropolitan Atlanta and south west Ohio, using live birth and prenatally diagnosed cases ascertained during 1970-1989. The f...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Huether CA,Ivanovich J,Goodwin BS,Krivchenia EL,Hertzberg VS,Edmonds LD,May DS,Priest JH

    更新日期:1998-06-01 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

  • Early prenatal diagnosis of Hurler's syndrome with termination of pregnancy and confirmatory findings on the fetus.

    abstract::Mucopolysaccharidosis Type I (Hurler's syndrome) was diagnosed in an 18 week old fetus of a woman with 1 affected child by direct assay of glycosaminoglycans in amniotic fluid. Subsequently the fetus was aborted by hysterotomy and diagnosis was confirmed by analyzing glycosaminoglycans in fetal liver, electron microg...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Crawfurd M,Dean MF,Hunt DM,Johnson DR,MacDonald RR,Muir H,Wright EA,Wright CR

    更新日期:1973-06-01 00:00:00

  • Submicroscopic deletions at 16p13.3 in Rubinstein-Taybi syndrome: frequency and clinical manifestations in a North American population.

    abstract::Rubinstein-Taybi syndrome (RTS) is a well delineated multiple congenital anomaly syndrome characterised by mental retardation, broad thumbs and toes, short stature, and specific facial features. The recent localisation of the disorder to 16p13.3 and subsequent identification of a submicroscopic deletion of this region...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Wallerstein R,Anderson CE,Hay B,Gupta P,Gibas L,Ansari K,Cowchock FS,Weinblatt V,Reid C,Levitas A,Jackson L

    更新日期:1997-03-01 00:00:00

  • Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease.

    abstract:BACKGROUND:Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. METHODS:The sample groups consisted of 180 AD patients and 141 control spouses. We carried out...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Cheng D,Huang R,Lanham IS,Cathcart HM,Howard M,Corder EH,Poduslo SE

    更新日期:2005-02-01 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


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

    更新日期:1992-01-01 00:00:00

  • Evaluation of information-guidance genetic counselling.

    abstract::The impact of information-guidance type of genetic counseling was evaluated for the family planning of 2082 consultands. The understanding of the risks, parental decision, and the number of induced and spontaneous abortions were evaluated by the use of questionnaires. The stillbirths, livebirths, infant deaths, and ba...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Czeizel A,Métneki J,Osztovics M

    更新日期:1981-04-01 00:00:00

  • Detecting low penetrance genes in cancer: the way ahead.

    abstract::The search for the genes responsible for many complex genetic diseases is well under way and has already been successful in some cases. The study of cancer as a complex genetic disease has lagged behind other conditions, largely because of particular problems that are associated with malignant disease. Cancer also, ho...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Houlston RS,Tomlinson IP

    更新日期:2000-03-01 00:00:00

  • Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families.

    abstract::We have performed an extensive analysis of TP53 in 474 French families suggestive of Li-Fraumeni syndrome (LFS), including 232 families fulfilling the Chompret criteria. We identified a germline alteration of TP53 in 82 families (17%), in 67/232 of the families fulfilling the Chompret criteria (29%) and in 15/242 whic...

    journal_title:Journal of medical genetics

    pub_type: 信件


    authors: Bougeard G,Sesboüé R,Baert-Desurmont S,Vasseur S,Martin C,Tinat J,Brugières L,Chompret A,de Paillerets BB,Stoppa-Lyonnet D,Bonaïti-Pellié C,Frébourg T,French LFS working group.

    更新日期:2008-08-01 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

  • The use of loss of constitutional heterozygosity data to ascertain the location of predisposing genes in cancer families.

    abstract::A method is described to investigate the inheritance of disease predisposition in cancer families. It is an extension of classic genetic linkage analysis, which enables information on loss of constitutional heterozygosity (LOCH) to be incorporated into the model. This adapted model treats LOCH data as additional obser...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Teare MD,Rohde K,Santibáñez Koref MF

    更新日期:1994-06-01 00:00:00

  • X mapping in man: evidence against direct measurable linkage between ocular albinism and deutan colour blindness.

    abstract::A Newfoundland kindred in which ocular albinism and deutan colour blindness are segregating provides strong evidence against the loci for these two X-borne characters being within direct measurable distance of each other. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Pearce WG,Sanger R

    更新日期:1976-08-01 00:00:00

  • Umbilical cord hernia in a child with autosomal recessive chondrodysplasia punctata.

    abstract::An infant with congenital chondrodysplasia punctata with a secondary deformation of umbilical cord hernia is reported. The paper discusses deformation syndromes as anomalies due to unusual mechanical or intrinsic factors. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Chandavasu O,Desposito F

    更新日期:1986-02-01 00:00:00

  • Unusual occurrence of cervical myelopathy in a case of Stickler's syndrome.

    abstract::We report the occurrence of progressive Brown-Séquard syndrome as the presenting clinical feature of cervical spondylosis in a young patient with Stickler's syndrome. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Noël S,Balériaux D,Telerman-Toppet N

    更新日期:1992-03-01 00:00:00

  • Clinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria.

    abstract:BACKGROUND:The clinical phenotype of CDH1 pathogenic variant carriers has mostly been studied in families that fulfil criteria of hereditary diffuse gastric cancer (HDGC). We aimed at determining cancer phenotype and cancer risk estimation among families with CDH1 pathogenic variants not selected by HDGC clinical crite...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Xicola RM,Li S,Rodriguez N,Reinecke P,Karam R,Speare V,Black MH,LaDuca H,Llor X

    更新日期:2019-12-01 00:00:00

  • Marfan syndrome in a large family: response of family members to a screening programme.

    abstract::Reaction to medical, social, and genetic implications of Marfan syndrome was evaluated by means of two questionnaires, the first after various tests before discussion of the diagnosis, the second after full discussion of the patient's diagnosis. Thirty-seven members of a family known to be at risk for Marfan syndrome ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Bridges AB,Faed M,Boxer M,Gray JR,Bundy C,Murray A

    更新日期:1992-02-01 00:00:00

  • Prenatal diagnosis of osteogenesis imperfecta by identification of the concordant collagen 1 allele.

    abstract::Dominantly inherited osteogenesis imperfecta is consistently linked to the two loci encoding the alpha 1 and alpha 2 subunits of collagen 1, the predominant bone collagen. We have performed several prenatal diagnoses based on identification of the segregating allele at the concordant locus in chorionic villus samples ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Lynch JR,Ogilvie D,Priestley L,Baigrie C,Smith R,Farndon P,Sykes B

    更新日期:1991-03-01 00:00:00

  • Homozygous hypomorphic BRCA2 variant in primary ovarian insufficiency without cancer or Fanconi anaemia trait.

    abstract:BACKGROUND:Primary ovarian insufficiency (POI) affects 1% of women under 40 years and is a public health problem. The genetic causes of POI are highly heterogeneous with isolated or syndromic forms. Recently, variants in genes involved in DNA repair have been shown to cause POI. Notably, syndromic POI with Fanconi anae...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Caburet S,Heddar A,Dardillac E,Creux H,Lambert M,Messiaen S,Tourpin S,Livera G,Lopez BS,Misrahi M

    更新日期:2020-06-01 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

  • A comprehensive strategy for the subtyping of patients with Fanconi anaemia: conclusions from the Spanish Fanconi Anemia Research Network.

    abstract:BACKGROUND:Fanconi anaemia is a heterogeneous genetic disease, where 12 complementation groups have been already described. Identifying the complementation group in patients with Fanconi anaemia constitutes a direct procedure to confirm the diagnosis of the disease and is required for the recruitment of these patients ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Antonio Casado J,Callén E,Jacome A,Río P,Castella M,Lobitz S,Ferro T,Muñoz A,Sevilla J,Cantalejo A,Cela E,Cervera J,Sánchez-Calero J,Badell I,Estella J,Dasí A,Olivé T,José Ortega J,Rodriguez-Villa A,Tapia M,Moliné

    更新日期:2007-04-01 00:00:00

  • Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

    abstract:BACKGROUND:Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS:Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Lavoine N,Colas C,Muleris M,Bodo S,Duval A,Entz-Werle N,Coulet F,Cabaret O,Andreiuolo F,Charpy C,Sebille G,Wang Q,Lejeune S,Buisine MP,Leroux D,Couillault G,Leverger G,Fricker JP,Guimbaud R,Mathieu-Dramard M,Jedra

    更新日期:2015-11-01 00:00:00

  • Postaxial acrofacial dysostosis (Miller) syndrome: a new case.

    abstract::We describe a new case of postaxial acrofacial dysostosis (Miller) syndrome. This syndrome consists of mandibulofacial dysostosis, similar to that seen in Treacher Collins syndrome, and postaxial limb deficiency. The mode of inheritance remains uncertain. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Vigneron J,Stricker M,Vert P,Rousselot JM,Levy M

    更新日期:1991-09-01 00:00:00

  • Topographic approach for analysis of palm crease variants.

    abstract::As the variability and possible clinical significance of palm increase abnormalities receive greater attention, an accurate and objective method for evaluating the palm increase variants is required. A new method is described employing a topographic approach. A network of co-ordinates drawn on the palm prints enables ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章


    authors: Dar H,Schmidt R

    更新日期:1976-08-01 00:00:00

  • Prenatal and postnatal growth failure associated with maternal heterodisomy for chromosome 7.

    abstract::The association of maternal uniparental disomy for chromosome 7 and postnatal growth failure has been reported in four cases and suggests the presence of genomic imprinting of one or more growth related genes on chromosome 7. However, in the reported cases, the possibility of homozygosity for a recessive mutation coul...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审


    authors: Langlois S,Yong SL,Wilson RD,Kwong LC,Kalousek DK

    更新日期:1995-11-01 00:00:00