GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY).


:Maturity onset diabetes of the young (MODY) is a genetically heterogeneous form of type 2 diabetes that is characterized by autosomal dominant inheritance, onset in early adulthood and a primary defect in insulin secretion. Mutations in at least six genes have been shown to underlie MODY, including mutations in GCK (encoding glucokinase, also called MODY2) and mutations in HNF1A (encoding hepatocyte nuclear factor-1alpha, also called MODY3). We sequenced genomic DNA from probands of seven Canadian MODY families. In four probands, we detected four novel GCK mutations, namely IVS2-7G>A, G72R, T206R and S263P. In three other probands, we detected three HNF1A mutations, of which two were novel, namely 1051delCA and Q250X, and one had been previously reported, namely R131Q. The novel mutations expand the spectrum of MODY mutations. In addition, knowledge of the specific defect can be used to pre-symptomatically identify family members at risk for developing MODY.


Hum Mutat


Human mutation


Cao H,Shorey S,Robinson J,Metzger DL,Stewart L,Cummings E,Hegele RA





Has Abstract


2002-12-01 00:00:00












  • Rapid classification of phenylketonuria genotypes by analysis of heteroduplexes generated by PCR-amplifiable synthetic DNA.

    abstract::We describe a rapid and simple method for phenylketonuria genotyping which identifies five point mutations within exon 12 of the human phenylalanine hydroxylase gene. The method involves PCR amplification of the target exon and hybridization with a PCR-amplifiable synthetic DNA (universal heteroduplex generator, UHG)....

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wood N,Tyfield L,Bidwell J

    更新日期:1993-01-01 00:00:00

  • RRBS-analyser: a comprehensive web server for reduced representation bisulfite sequencing data analysis.

    abstract::In reduced representation bisulfite sequencing (RRBS), genomic DNA is digested with the restriction enzyme and then subjected to next-generation sequencing, which enables detection and quantification of DNA methylation at whole-genome scale with low cost. However, the data processing, interpretation, and analysis of t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wang T,Liu Q,Li X,Wang X,Li J,Zhu X,Sun ZS,Wu J

    更新日期:2013-12-01 00:00:00

  • Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrier-screening test.

    abstract::Autosomal recessive spinal muscular atrophy (SMA) is a common, fatal neuromuscular disease caused by homozygous absence of the SMN1 gene in approximately 94% of patients. However, a highly homologous SMN2 gene exists in the same chromosome interval, centromeric to SMN1, and hampers detection of SMN1. We present a new,...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Su YN,Hung CC,Li H,Lee CN,Cheng WF,Tsao PN,Chang MC,Yu CL,Hsieh WS,Lin WL,Hsu SM

    更新日期:2005-05-01 00:00:00

  • Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies.

    abstract::Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA se...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Patrinos GP,Kollia P,Papadakis MN

    更新日期:2005-11-01 00:00:00

  • Mutation update: TGFBI pathogenic and likely pathogenic variants in corneal dystrophies.

    abstract::Human transforming growth factor β-induced (TGFBI), is a gene responsible for various corneal dystrophies. TGFBI produces a protein called TGFBI, which is involved in cell adhesion and serves as a recognition sequence for integrins. An alteration in cell surface interactions could be the underlying cause for the progr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kheir V,Cortés-González V,Zenteno JC,Schorderet DF

    更新日期:2019-06-01 00:00:00

  • The evaluation of tools used to predict the impact of missense variants is hindered by two types of circularity.

    abstract::Prioritizing missense variants for further experimental investigation is a key challenge in current sequencing studies for exploring complex and Mendelian diseases. A large number of in silico tools have been employed for the task of pathogenicity prediction, including PolyPhen-2, SIFT, FatHMM, MutationTaster-2, Mutat...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Grimm DG,Azencott CA,Aicheler F,Gieraths U,MacArthur DG,Samocha KE,Cooper DN,Stenson PD,Daly MJ,Smoller JW,Duncan LE,Borgwardt KM

    更新日期:2015-05-01 00:00:00

  • Pyrosequencing: an accurate detection platform for single nucleotide polymorphisms.

    abstract::Pyrosequencing, a non-electrophoretic method for DNA sequencing, is emerging as a popular platform for analysis of single nucleotide polymorphisms (SNPs). This technology has the advantage of accuracy, ease-of-use, and high flexibility for different applications. Here, we review the methodology and the use of this tec...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Fakhrai-Rad H,Pourmand N,Ronaghi M

    更新日期:2002-05-01 00:00:00

  • Severity of X-linked dyskeratosis congenita (DKCX) cellular defects is not directly related to dyskerin (DKC1) activity in ribosomal RNA biogenesis or mRNA translation.

    abstract::Dyskerin (encoded by the DKC1 locus) is the pseudouridine synthase responsible for the modification of noncoding RNA. Dyskerin is also an obligate member of the telomerase enzyme, and participates in the biogenesis of telomerase. Genetic lesions at the DKC1 locus are associated with X-linked dyskeratosis congenita (X-...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Thumati NR,Zeng XL,Au HH,Jang CJ,Jan E,Wong JM

    更新日期:2013-12-01 00:00:00

  • Performance of computational methods for the evaluation of pericentriolar material 1 missense variants in CAGI-5.

    abstract::The CAGI-5 pericentriolar material 1 (PCM1) challenge aimed to predict the effect of 38 transgenic human missense mutations in the PCM1 protein implicated in schizophrenia. Participants were provided with 16 benign variants (negative controls), 10 hypomorphic, and 12 loss of function variants. Six groups participated ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Monzon AM,Carraro M,Chiricosta L,Reggiani F,Han J,Ozturk K,Wang Y,Miller M,Bromberg Y,Capriotti E,Savojardo C,Babbi G,Martelli PL,Casadio R,Katsonis P,Lichtarge O,Carter H,Kousi M,Katsanis N,Andreoletti G,Moult J

    更新日期:2019-09-01 00:00:00

  • Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation.

    abstract::Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. We report the molecular characterization of a de novo balanced t(2;7)(q37.1;q21.3) tr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bocciardi R,Giorda R,Buttgereit J,Gimelli S,Divizia MT,Beri S,Garofalo S,Tavella S,Lerone M,Zuffardi O,Bader M,Ravazzolo R,Gimelli G

    更新日期:2007-07-01 00:00:00

  • Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease.

    abstract::Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib-polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer-Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by m...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schmidts M,Frank V,Eisenberger T,Al Turki S,Bizet AA,Antony D,Rix S,Decker C,Bachmann N,Bald M,Vinke T,Toenshoff B,Di Donato N,Neuhann T,Hartley JL,Maher ER,Bogdanović R,Peco-Antić A,Mache C,Hurles ME,Joksić I,G

    更新日期:2013-05-01 00:00:00

  • Rapid detection of exon 1 NRAS gene mutations using universal heteroduplex generator technology.

    abstract::Specific NRAS oncogene missense mutations have been frequently found in some tumors and several hematological diseases, especially in those of myeloid origin. There is a wide range of PCR-based methods for screening and detection of NRAS exon 1 single-base substitutions. However, there are disadvantages and ambiguitie...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Belli C,De Brasi C,Larripa I

    更新日期:2003-02-01 00:00:00

  • Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2 Deletion Syndrome Family Trios for Genotype to Phenotype Correlations.

    abstract::The 22q11.2 deletion syndrome (22q11DS) affects 1:4,000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole-genome sequencing (WGS) and integrative analysis to discover genetic modifiers. Our pipeline combined available tools in order...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chung JH,Cai J,Suskin BG,Zhang Z,Coleman K,Morrow BE

    更新日期:2015-08-01 00:00:00

  • Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online.

    abstract::Inactivation of the adenomatous polyposis coli (APC) gene is an early event in sporadic colorectal cancer. Somatic mutations have also been detected in cancers of the stomach, pancreas, thyroid, ovary and breast. Over 95% of the mutations reported in the APC gene are frameshift and nonsense mutations. The large exon 1...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sørlie T,Bukholm I,Børresen-Dale AL

    更新日期:1998-01-01 00:00:00

  • VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: the first description of a VAX1 phenotype in humans.

    abstract::Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Slavotinek AM,Chao R,Vacik T,Yahyavi M,Abouzeid H,Bardakjian T,Schneider A,Shaw G,Sherr EH,Lemke G,Youssef M,Schorderet DF

    更新日期:2012-02-01 00:00:00

  • MouseFinder: Candidate disease genes from mouse phenotype data.

    abstract::Mouse phenotype data represents a valuable resource for the identification of disease-associated genes, especially where the molecular basis is unknown and there is no clue to the candidate gene's function, pathway involvement or expression pattern. However, until recently these data have not been systematically used ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen CK,Mungall CJ,Gkoutos GV,Doelken SC,Köhler S,Ruef BJ,Smith C,Westerfield M,Robinson PN,Lewis SE,Schofield PN,Smedley D

    更新日期:2012-05-01 00:00:00

  • Allele-specific competitive blocker PCR: a one-step method with applicability to pool screening.

    abstract::We have developed a novel one-step pool screening PCR procedure which is based on the principles of amplification refractory mutation system (ARMS) and competitive oligonuleotide priming (COP) PCR. In addition to the usual primers, this approach uses two allele-specific competitive oligonucleotides, one of which is 3'...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Orou A,Fechner B,Utermann G,Menzel HJ

    更新日期:1995-01-01 00:00:00

  • CACNA1H variants are not a cause of monogenic epilepsy.

    abstract::CACNA1H genetic variants were originally reported in a childhood absence epilepsy cohort. Subsequently, genetic testing for CACNA1H became available and is currently offered by commercial laboratories. However, the current status of CACNA1H as a monogenic cause of epilepsy is controversial, highlighted by ClinGen's re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Calhoun JD,Huffman AM,Bellinski I,Kinsley L,Bachman E,Gerard E,Kearney JA,Carvill GL

    更新日期:2020-06-01 00:00:00

  • Genetic variants of ABCA1 modify Alzheimer disease risk and quantitative traits related to beta-amyloid metabolism.

    abstract::Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central rol...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Katzov H,Chalmers K,Palmgren J,Andreasen N,Johansson B,Cairns NJ,Gatz M,Wilcock GK,Love S,Pedersen NL,Brookes AJ,Blennow K,Kehoe PG,Prince JA

    更新日期:2004-04-01 00:00:00

  • Determination of variants in the 3'-region of the tyrosinase gene requires locus specific amplification.

    abstract::Mutations in the Tyrosinase gene (TYR, 11q14-q21) cause oculocutaneous albinism type 1 (OCA1). The 3'-region of the TYR shows 98.55% sequence identity with a pseudogene, known as Tyrosinase-Like Gene (TYRL, 11p11.2-cen). A large number of publicly available nucleotide variants of TYR in this region are same as the bas...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chaki M,Mukhopadhyay A,Ray K

    更新日期:2005-07-01 00:00:00

  • Transthyretin mutations in health and disease.

    abstract::To date, over 40 different mutations in transthyretin (TTR) have been associated with amyloid deposition. The major unresolved problem is the correlation between the clinical heterogeneity and the genetic heterogeneity. For instance, whereas some mutations produce neuropathy and some give rise to cardiomyopathy, other...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Saraiva MJ

    更新日期:1995-01-01 00:00:00

  • Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

    abstract::Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is c...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Denora PS,Schlesinger D,Casali C,Kok F,Tessa A,Boukhris A,Azzedine H,Dotti MT,Bruno C,Truchetto J,Biancheri R,Fedirko E,Di Rocco M,Bueno C,Malandrini A,Battini R,Sickl E,de Leva MF,Boespflug-Tanguy O,Silvestri G,S

    更新日期:2009-03-01 00:00:00

  • A new glucose 6 phosphate dehydrogenase variant G6PD Sinnai (34 G-->T). Mutations in brief no. 156. Online.

    abstract::In this paper we report a male infant heterozygous for thalassemia with a mild glucose 6 phosphate dehydrogenase deficiency. The molecular basis of this new Class III G6PD variant is a G-->T mutation at nucleotide 34 in the exon 2, which predicts a Val-->Leu aminoacid substitution at codon 12. We designated this varia...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Galanello R,Loi D,Sollaino C,Dessì S,Cao A,Melis MA

    更新日期:1998-01-01 00:00:00

  • A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region.

    abstract::A high proportion of patients with late onset forms of Krabbe disease is observed in a region north of Catania in Sicily. Molecular analysis in five families from this region shows that this condition is mainly due to a not previously described p.Gly41Ser substitution in the GALC gene that abolishes catalytic activity...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lissens W,Arena A,Seneca S,Rafi M,Sorge G,Liebaers I,Wenger D,Fiumara A

    更新日期:2007-07-01 00:00:00

  • Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study.

    abstract::We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first ...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Tan EK,Peng R,Teo YY,Tan LC,Angeles D,Ho P,Chen ML,Lin CH,Mao XY,Chang XL,Prakash KM,Liu JJ,Au WL,Le WD,Jankovic J,Burgunder JM,Zhao Y,Wu RM

    更新日期:2010-05-01 00:00:00

  • NSD1 PHD domains bind methylated H3K4 and H3K9 using interactions disrupted by point mutations in human sotos syndrome.

    abstract::Sotos syndrome is a human developmental and cognitive disorder caused by happloinsufficiency of transcription factor NSD1. Similar phenotypes arise from NSD1 gene deletion or from point mutations in 9 of 13 NSD1 domains, including all 6 PHD domains, indicating that each NSD1 domain performs an essential role. To gain ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pasillas MP,Shah M,Kamps MP

    更新日期:2011-03-01 00:00:00

  • The 2004 Human Genome Variation Society scientific meeting.

    abstract::The Human Genome Variation Society annual scientific meeting was held on 26 October 2004 in Toronto, Canada, and attracted 85 registrants. Meeting participants from 14 countries reported on the recent advances and progress made toward the detection, analysis, and documentation of genetic variation. Reports were made o...

    journal_title:Human mutation



    authors: Oetting WS,Tabone T

    更新日期:2005-08-01 00:00:00

  • STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.

    abstract::SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a pati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zaharieva IT,Sarkozy A,Munot P,Manzur A,O'Grady G,Rendu J,Malfatti E,Amthor H,Servais L,Urtizberea JA,Neto OA,Zanoteli E,Donkervoort S,Taylor J,Dixon J,Poke G,Foley AR,Holmes C,Williams G,Holder M,Yum S,Medne L

    更新日期:2018-12-01 00:00:00

  • GALNT12 is not a major contributor of familial colorectal cancer type X.

    abstract::Previous evidence indicates that mutations in the GALNT12 gene might cause a fraction of the unexplained familial colorectal cancer (CRC) cases: GALNT12 is located in 9q22-33, in close proximity to a CRC linkage peak; and germline missense variants that reduce the enzymatic activity of the protein have been identified...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Seguí N,Pineda M,Navarro M,Lázaro C,Brunet J,Infante M,Durán M,Soto JL,Blanco I,Capellá G,Valle L

    更新日期:2014-01-01 00:00:00

  • Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes.

    abstract::The Marfan (MFS) and Loeys-Dietz (LDS) syndromes are caused by mutations in the fibrillin-1 (FBN1) and Transforming Growth Factor Beta Receptor 1 and 2 (TGFBR1 and TGFBR2) genes, respectively. With the current conventional mutation screening technologies, analysis of this set of genes is time consuming and expensive. ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Baetens M,Van Laer L,De Leeneer K,Hellemans J,De Schrijver J,Van De Voorde H,Renard M,Dietz H,Lacro RV,Menten B,Van Criekinge W,De Backer J,De Paepe A,Loeys B,Coucke PJ

    更新日期:2011-09-01 00:00:00