L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1.


:l-2-Hydroxyglutaric aciduria (l-2-HGA) is characterized by progressive deterioration of central nervous system function including epilepsy and macrocephaly in 50% of cases, and elevated levels of l-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). Nuclear magnetic resonance imaging shows distinct abnormalities. We report the identification of a gene for l-2-HGA aciduria (MIM 236792) using homozygosity mapping. Nine homozygous mutations including three missense mutations, two nonsense mutations, two splice site mutations and two deletions were identified in the gene C14orf160, localized on chromosome 14q22.1, in 21 patients from one non-consanguineous and 14 consanguineous Turkish families. We propose to name the gene duranin. Duranin encodes a putative mitochondrial protein with homology to FAD-dependent oxidoreductases. The functional role of this enzyme in intermediary metabolism in humans remains to be established.


Hum Mol Genet


Human molecular genetics


Topçu M,Jobard F,Halliez S,Coskun T,Yalçinkayal C,Gerceker FO,Wanders RJ,Prud'homme JF,Lathrop M,Ozguc M,Fischer J




Has Abstract


2004-11-15 00:00:00














  • A single allele from the polymorphic CCG rich sequence immediately 3' to the unstable CAG trinucleotide in the IT15 cDNA shows almost complete disequilibrium with Huntington's disease chromosomes in the Scottish population.

    abstract::The CCG rich sequence immediately 3' to the CAG repeat that is expanded in Huntington's disease (HD) has recently been shown to be polymorphic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 180 HD families resident in Scotland and...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Barron LH,Rae A,Holloway S,Brock DJ,Warner JP

    更新日期:1994-01-01 00:00:00

  • Functional assessment of variants associated with Wolfram syndrome.

    abstract::Wolfram syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and ne...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Riachi M,Yilmaz S,Kurnaz E,Aycan Z,Çetinkaya S,Tranebjærg L,Rendtorff ND,Bitner-Glindzicz M,Bockenhauer D,Hussain K

    更新日期:2019-11-15 00:00:00

  • Circulating microRNAs as potential biomarkers of disease activity and structural damage in ankylosing spondylitis patients.

    abstract::Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of mi...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Perez-Sanchez C,Font-Ugalde P,Ruiz-Limon P,Lopez-Pedrera C,Castro-Villegas MC,Abalos-Aguilera MC,Barbarroja N,Arias-de la Rosa I,Lopez-Montilla MD,Escudero-Contreras A,Lopez-Medina C,Collantes-Estevez E,Jimenez-Gomez Y

    更新日期:2018-03-01 00:00:00

  • Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia.

    abstract::Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotid...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Dols-Icardo O,García-Redondo A,Rojas-García R,Sánchez-Valle R,Noguera A,Gómez-Tortosa E,Pastor P,Hernández I,Esteban-Pérez J,Suárez-Calvet M,Antón-Aguirre S,Amer G,Ortega-Cubero S,Blesa R,Fortea J,Alcolea D,Capdevila A,

    更新日期:2014-02-01 00:00:00

  • C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity.

    abstract::P/Q-type voltage-gated calcium channels are regulated, in part, through the cytoplasmic C-terminus of their alpha1A subunit. Genetic absence or alteration of the C-terminus leads to abnormal channel function and neurological disease. Here, we show that the terminal 60-75 kDa of the endogenous alpha1A C-terminus is cle...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Kordasiewicz HB,Thompson RM,Clark HB,Gomez CM

    更新日期:2006-05-15 00:00:00

  • Expression of C9orf72-related dipeptides impairs motor function in a vertebrate model.

    abstract::Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Different hypotheses exist about the...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Swaminathan A,Bouffard M,Liao M,Ryan S,Callister JB,Pickering-Brown SM,Armstrong GAB,Drapeau P

    更新日期:2018-05-15 00:00:00

  • Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy.

    abstract::Myotonic dystrophy type I (DM1) is an RNA-mediated disease caused by a non-coding CTG repeat expansion. A key feature of the RNA-mediated pathogenesis model for DM is the disrupted splicing of specific pre-mRNA targets. A link has been established between splicing regulation by CUG-BP1, a member of the CELF family of ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ho TH,Bundman D,Armstrong DL,Cooper TA

    更新日期:2005-06-01 00:00:00

  • Polar substitutions in helix 3 of the prion protein produce transmembrane isoforms that disturb vesicle trafficking.

    abstract::Prion diseases encompass a diverse group of neurodegenerative conditions characterized by the accumulation of misfolded prion protein (PrP) isoforms. Other conformational variants of PrP have also been proposed to contribute to neurotoxicity in prion diseases, including misfolded intermediates as well as cytosolic and...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Sanchez-Garcia J,Arbelaez D,Jensen K,Rincon-Limas DE,Fernandez-Funez P

    更新日期:2013-11-01 00:00:00

  • Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles.

    abstract::Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Laufer BI,Hwang H,Jianu JM,Mordaunt CE,Korf IF,Hertz-Picciotto I,LaSalle JM

    更新日期:2021-01-06 00:00:00

  • Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.

    abstract::Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are two human autosomal dominant skeletal dysplasias characterized by variable short stature, joint laxity and early-onset degenerative joint disease. Both disorders can result from mut-ations in the gene for cartilage oligomeric matrix protein (COMP...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Délot E,King LM,Briggs MD,Wilcox WR,Cohn DH

    更新日期:1999-01-01 00:00:00

  • The selective footprints of viral pressures at the human RIG-I-like receptor family.

    abstract::The RIG-I-like receptors (RLRs)--RIG-I, IFIH1 (or MDA5) and LGP2--are thought to be key actors in the innate immune system, as they play a major role in sensing RNA viruses in the cytosol of host cells. Despite the increasingly recognized importance of the RLR family in antiviral immunity, no population genetic studie...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Vasseur E,Patin E,Laval G,Pajon S,Fornarino S,Crouau-Roy B,Quintana-Murci L

    更新日期:2011-11-15 00:00:00

  • Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.

    abstract::The early growth response 2 gene ( EGR2 ) is a Cys2His2zinc finger transcription factor which is thought to play a role in the regulation of peripheral nervous system myelination. This idea is based partly on the phenotype of homozygous Krox20 ( Egr2 ) knockout mice, which display hypomyelination of the PNS and a bloc...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Warner LE,Svaren J,Milbrandt J,Lupski JR

    更新日期:1999-07-01 00:00:00

  • Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

    abstract::Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,meta分析


    authors: Zhang L,Choi HJ,Estrada K,Leo PJ,Li J,Pei YF,Zhang Y,Lin Y,Shen H,Liu YZ,Liu Y,Zhao Y,Zhang JG,Tian Q,Wang YP,Han Y,Ran S,Hai R,Zhu XZ,Wu S,Yan H,Liu X,Yang TL,Guo Y,Zhang F,Guo YF,Chen Y,Chen X,Ta

    更新日期:2014-04-01 00:00:00

  • Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.

    abstract::Spinal muscular atrophy (SMA) is a common pediatric neuromuscular disorder caused by insufficient levels of the survival of motor neuron (SMN) protein. Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Kariya S,Park GH,Maeno-Hikichi Y,Leykekhman O,Lutz C,Arkovitz MS,Landmesser LT,Monani UR

    更新日期:2008-08-15 00:00:00

  • Genomic structure and parent-of-origin-specific methylation of Peg1.

    abstract::We previously identified Peg1/Mest as a novel paternally expressed gene in the developing mouse embryo. The human PEG1 gene was recently assigned to 7q32 and shown to be imprinted and paternally expressed. Therefore, PEG1 deficiency could participate in the aetiology of pre- and post-natal growth retardation associate...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lefebvre L,Viville S,Barton SC,Ishino F,Surani MA

    更新日期:1997-10-01 00:00:00

  • Downstream targets of GWAS-detected genes for breast, lung, and prostate and colon cancer converge to G1/S transition pathway.

    abstract::Genome-wide association studies (GWASs) identified over 500 single nucleotide polymorphisms (SNPs) influencing cancer risk. It is logical to expect the cancer-associated genes to cluster in pathways directly involved in carcinogenesis, e.g. cell cycle. Nevertheless, analyses of the GWAS-detected cancer risk genes usua...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Gorlova OY,Demidenko EI,Amos CI,Gorlov IP

    更新日期:2017-04-15 00:00:00

  • HSC20 interacts with frataxin and is involved in iron-sulfur cluster biogenesis and iron homeostasis.

    abstract::Friedreich's ataxia is a neurodegenerative disorder caused by mutations in the frataxin gene that produces a predominantly mitochondrial protein whose primary function appears to be mitochondrial iron-sulfur cluster (ISC) biosynthesis. Previously we demonstrated that frataxin interacts with multiple components of the ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Shan Y,Cortopassi G

    更新日期:2012-04-01 00:00:00

  • Chemical genetics unveils a key role of mitochondrial dynamics, cytochrome c release and IP3R activity in muscular dystrophy.

    abstract::Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. The subcellular mechanisms of DMD remain poorly understood and there is currently no curative treatment available. Using a Caenorhabditis elegans model for DMD as a pharmacologic and genetic tool, we found that cyc...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Giacomotto J,Brouilly N,Walter L,Mariol MC,Berger J,Ségalat L,Becker TS,Currie PD,Gieseler K

    更新日期:2013-11-15 00:00:00

  • Construction of a YAC contig and a STS map spanning at least seven megabasepairs in chromosome 5q34-35.

    abstract::We have constructed a YAC contig containing 54 clones and a minimum of 7 Mbp of human DNA, that maps to bands q34-35 on chromosome 5. The contig was nucleated using FISH mapped cosmid clones shown to flank the t(2;5)(p23;q35) translocation breakpoint in a CD30-positive large cell lymphoma cell line. Thirty of the 54 Y...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lu-Kuo JM,Le Paslier D,Weissenbach J,Chumakov I,Cohen D,Ward DC

    更新日期:1994-01-01 00:00:00

  • Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue.

    abstract::Fourteen neurological diseases have been associated with the expansion of trinucleotide repeat regions. These diseases have been categorized into those that give rise to the translation of toxic polyglutamine proteins and those that are untranslated. Thus far, compelling evidence has not surfaced for the inclusion of ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Peel AL,Rao RV,Cottrell BA,Hayden MR,Ellerby LM,Bredesen DE

    更新日期:2001-07-15 00:00:00

  • Cloning and characterization of the human choroideremia gene.

    abstract::Positional cloning has previously resulted in the identification of a gene which is disrupted by deletions in patients with the classic choroideremia (CHM) phenotype. More subtle mutations had been identified in 4 exons of the 3' portion but not elsewhere in the CHM gene. We have now isolated and characterized the com...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: van Bokhoven H,van den Hurk JA,Bogerd L,Philippe C,Gilgenkrantz S,de Jong P,Ropers HH,Cremers FP

    更新日期:1994-07-01 00:00:00

  • Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region.

    abstract::An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, ot...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Chartier-Harlin MC,Parfitt M,Legrain S,Pérez-Tur J,Brousseau T,Evans A,Berr C,Vidal O,Roques P,Gourlet V

    更新日期:1994-04-01 00:00:00

  • Ataxin-2 and huntingtin interact with endophilin-A complexes to function in plastin-associated pathways.

    abstract::Spinocerebellar ataxia type 2 is an inherited neurodegenerative disorder that is caused by an expanded trinucleotide repeat in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2. Although evidence has been provided that ataxin-2 is involved in RNA metabolism, the physiological function of ata...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ralser M,Nonhoff U,Albrecht M,Lengauer T,Wanker EE,Lehrach H,Krobitsch S

    更新日期:2005-10-01 00:00:00

  • Population genetics of trinucleotide repeat polymorphisms.

    abstract::Trinucleotide repeats at five disease loci (DM, DRPLA, HD, SBMA and SCA1) were surveyed in phenotypically normal individuals from three continental populations. This is the first analysis to examine the population dynamics of these five disease-related trinucleotide repeats in the same individuals from worldwide popul...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Watkins WS,Bamshad M,Jorde LB

    更新日期:1995-09-01 00:00:00

  • Strategies to prevent cleavage of the linker region between ligand-binding repeats 4 and 5 of the LDL receptor.

    abstract::A main strategy for lowering plasma low-density lipoprotein (LDL) cholesterol levels is to increase the number of cell-surface LDL receptors (LDLRs). This can be achieved by increasing the synthesis or preventing the degradation of the LDLR. One mechanism by which an LDLR becomes non-functional is enzymatic cleavage w...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Strøm TB,Bjune K,Costa LTD,Leren TP

    更新日期:2019-11-15 00:00:00

  • Haplotype analysis of MEN 2 mutations.

    abstract::Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome which affects thyroid C cells, and with variable frequency, the adrenal medulla, parathyroid and enteric autonomic ganglia. The syndrome is due to germline mutation in the receptor tyrosine kinase gene, RET. We have recently shown an...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Gardner E,Mulligan LM,Eng C,Healey CS,Kwok JB,Ponder MA,Ponder BA

    更新日期:1994-10-01 00:00:00

  • Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease.

    abstract::Sphingosine-1-phosphate (S1P) is a lipid-signaling molecule produced by sphingosine kinase in response to a wide number of stimuli. By acting through a family of widely expressed G protein-coupled receptors, S1P regulates diverse physiological processes. Here we examined the role of S1P signaling in neurodegeneration ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wu YP,Mizugishi K,Bektas M,Sandhoff R,Proia RL

    更新日期:2008-08-01 00:00:00

  • Ca2+-permeable TRPV1 pain receptor knockout rescues memory deficits and reduces amyloid-β and tau in a mouse model of Alzheimer's disease.

    abstract::The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Kim J,Lee S,Kim J,Ham S,Park JHY,Han S,Jung YK,Shim I,Han JS,Lee KW,Kim J

    更新日期:2020-01-15 00:00:00

  • Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study.

    abstract::A susceptibility locus for coronary artery disease (CAD) at chromosome 9p21 has recently been reported, which may influence the age of onset of CAD. We sought to replicate these findings among white subjects and to examine whether these results are consistent with other racial/ethnic groups by genotyping three single ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Assimes TL,Knowles JW,Basu A,Iribarren C,Southwick A,Tang H,Absher D,Li J,Fair JM,Rubin GD,Sidney S,Fortmann SP,Go AS,Hlatky MA,Myers RM,Risch N,Quertermous T

    更新日期:2008-08-01 00:00:00

  • Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene.

    abstract::Psoriasis is an immune-mediated skin disorder that is inherited as a multifactorial trait. Linkage studies have clearly identified a primary disease susceptibility locus lying within the major histocompatibility complex (MHC), but have generated conflicting results for other genomic regions. To overcome this difficult...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Capon F,Bijlmakers MJ,Wolf N,Quaranta M,Huffmeier U,Allen M,Timms K,Abkevich V,Gutin A,Smith R,Warren RB,Young HS,Worthington J,Burden AD,Griffiths CE,Hayday A,Nestle FO,Reis A,Lanchbury J,Barker JN,Trembath RC

    更新日期:2008-07-01 00:00:00