当前位置： SCI文献检索 > NATURE GENETICS期刊下所有文献 > ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome.

ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome.

Abstract：

:Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect in laminin-binding glycan synthesis1. Although mutations in six genes have been identified as causes of WWS, only half of all individuals with the disease can currently be diagnosed on this basis2. A cell fusion complementation assay in fibroblasts from undiagnosed individuals with WWS was used to identify five new complementation groups. Further evaluation of one group by linkage analysis and targeted sequencing identified recessive mutations in the ISPD gene (encoding isoprenoid synthase domain containing). The pathogenicity of the identified ISPD mutations was shown by complementation of fibroblasts with wild-type ISPD. Finally, we show that recessive mutations in ISPD abolish the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. This establishes a new mechanism for WWS pathophysiology.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Willer T,Lee H,Lommel M,Yoshida-Moriguchi T,de Bernabe DB,Venzke D,Cirak S,Schachter H,Vajsar J,Voit T,Muntoni F,Loder AS,Dobyns WB,Winder TL,Strahl S,Mathews KD,Nelson SF,Moore SA,Campbell KP

doi

10.1038/ng.2252

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

575-80

issue

5

eissn

1061-4036

issn

1546-1718

pii

ng.2252

journal_volume

44

pub_type

杂志文章

相关文献

NATURE GENETICS文献大全
  • A multitrait GWAS sheds light on insulin resistance.

    abstract：:A genome-wide study of fasting insulin, HDL cholesterol and triglycerides, designed to depict insulin resistance, identified 53 independent loci associated with a limited capacity to store fat in a healthy way. The increased power of this multitrait approach provides insights into an otherwise difficult-to-grasp pheno...

    journal_title：Nature genetics

    pub_type： 评论,杂志文章

    doi：10.1038/ng.3758

    authors： Heid IM,Winkler TW

    更新日期：2016-12-28 00:00:00

  • Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

    abstract：:Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 ca...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/10297

    authors： Halushka MK,Fan JB,Bentley K,Hsie L,Shen N,Weder A,Cooper R,Lipshutz R,Chakravarti A

    更新日期：1999-07-01 00:00:00

  • Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.

    abstract：:Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide ass...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3340

    authors： Usher CL,Handsaker RE,Esko T,Tuke MA,Weedon MN,Hastie AR,Cao H,Moon JE,Kashin S,Fuchsberger C,Metspalu A,Pato CN,Pato MT,McCarthy MI,Boehnke M,Altshuler DM,Frayling TM,Hirschhorn JN,McCarroll SA

    更新日期：2015-08-01 00:00:00

  • Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.

    abstract：:Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-fu...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2950

    authors： Fontebasso AM,Papillon-Cavanagh S,Schwartzentruber J,Nikbakht H,Gerges N,Fiset PO,Bechet D,Faury D,De Jay N,Ramkissoon LA,Corcoran A,Jones DT,Sturm D,Johann P,Tomita T,Goldman S,Nagib M,Bendel A,Goumnerova L,Bowers

    更新日期：2014-05-01 00:00:00

  • Quantifying influenza virus diversity and transmission in humans.

    abstract：:Influenza A virus is characterized by high genetic diversity. However, most of what is known about influenza evolution has come from consensus sequences sampled at the epidemiological scale that only represent the dominant virus lineage within each infected host. Less is known about the extent of within-host virus div...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3479

    authors： Poon LL,Song T,Rosenfeld R,Lin X,Rogers MB,Zhou B,Sebra R,Halpin RA,Guan Y,Twaddle A,DePasse JV,Stockwell TB,Wentworth DE,Holmes EC,Greenbaum B,Peiris JS,Cowling BJ,Ghedin E

    更新日期：2016-02-01 00:00:00

  • BAP1 loss defines a new class of renal cell carcinoma.

    abstract：:The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitina...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2323

    authors： Peña-Llopis S,Vega-Rubín-de-Celis S,Liao A,Leng N,Pavía-Jiménez A,Wang S,Yamasaki T,Zhrebker L,Sivanand S,Spence P,Kinch L,Hambuch T,Jain S,Lotan Y,Margulis V,Sagalowsky AI,Summerour PB,Kabbani W,Wong SW,Grishin N,

    更新日期：2012-06-10 00:00:00

  • Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens.

    abstract：:Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftrm1HGU mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkhold...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0495-351

    authors： Davidson DJ,Dorin JR,McLachlan G,Ranaldi V,Lamb D,Doherty C,Govan J,Porteous DJ

    更新日期：1995-04-01 00:00:00

  • Discovery of common variants associated with low TSH levels and thyroid cancer risk.

    abstract：:To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer....

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.1046

    authors： Gudmundsson J,Sulem P,Gudbjartsson DF,Jonasson JG,Masson G,He H,Jonasdottir A,Sigurdsson A,Stacey SN,Johannsdottir H,Helgadottir HT,Li W,Nagy R,Ringel MD,Kloos RT,de Visser MC,Plantinga TS,den Heijer M,Aguillo E,Pan

    更新日期：2012-01-22 00:00:00

  • Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma.

    abstract：:Although nearly half of human melanomas harbor oncogenic BRAF(V600E) mutations, the genetic events that cooperate with these mutations to drive melanogenesis are still largely unknown. Here we show that Sleeping Beauty (SB) transposon-mediated mutagenesis drives melanoma progression in Braf(V600E) mutant mice and iden...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3275

    authors： Mann MB,Black MA,Jones DJ,Ward JM,Yew CC,Newberg JY,Dupuy AJ,Rust AG,Bosenberg MW,McMahon M,Print CG,Copeland NG,Jenkins NA

    更新日期：2015-05-01 00:00:00

  • A reference genome for pea provides insight into legume genome evolution.

    abstract：:We report the first annotated chromosome-level reference genome assembly for pea, Gregor Mendel's original genetic model. Phylogenetics and paleogenomics show genomic rearrangements across legumes and suggest a major role for repetitive elements in pea genome evolution. Compared to other sequenced Leguminosae genomes,...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-019-0480-1

    authors： Kreplak J,Madoui MA,Cápal P,Novák P,Labadie K,Aubert G,Bayer PE,Gali KK,Syme RA,Main D,Klein A,Bérard A,Vrbová I,Fournier C,d'Agata L,Belser C,Berrabah W,Toegelová H,Milec Z,Vrána J,Lee H,Kougbeadjo A,Térézol

    更新日期：2019-09-01 00:00:00

  • GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.

    abstract：:Glutamate receptors are well-known actors in the central and peripheral nervous systems, and altered glutamate signaling is implicated in several neurological and psychiatric disorders. It is increasingly recognized that such receptors may also have a role in tumor growth. Here we provide direct evidence of aberrant g...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2927

    authors： Nord KH,Lilljebjörn H,Vezzi F,Nilsson J,Magnusson L,Tayebwa J,de Jong D,Bovée JV,Hogendoorn PC,Szuhai K

    更新日期：2014-05-01 00:00:00

  • A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling.

    abstract：:PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1415

    authors： Ding H,Wu X,Boström H,Kim I,Wong N,Tsoi B,O'Rourke M,Koh GY,Soriano P,Betsholtz C,Hart TC,Marazita ML,Field LL,Tam PP,Nagy A

    更新日期：2004-10-01 00:00:00

  • Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.

    abstract：:An earlier search in the human, mouse and rat genomes for sequences that are 100% conserved in orthologous segments and > or = 200 bp in length identified 481 distinct sequences. These human-mouse-rat sequences, which represent ultraconserved elements (UCEs), are believed to be important for functions involving DNA bi...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1888

    authors： Derti A,Roth FP,Church GM,Wu CT

    更新日期：2006-10-01 00:00:00

  • Mutations in SDHC cause autosomal dominant paraganglioma, type 3.

    abstract：:Nonchromaffin paragangliomas (PGLs) are usually benign, neural-crest-derived, slow-growing tumours of parasympathetic ganglia. Between 10% and 50% of cases are familial and are transmitted as autosomal dominant traits with incomplete and age-dependent penetrance. ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/81551

    authors： Niemann S,Müller U

    更新日期：2000-11-01 00:00:00

  • DNA repair mediated by endonuclease-independent LINE-1 retrotransposition.

    abstract：:Long interspersed elements (LINE-1s) are abundant retrotransposons in mammalian genomes that probably retrotranspose by target site-primed reverse transcription (TPRT). During TPRT, the LINE-1 endonuclease cleaves genomic DNA, freeing a 3' hydroxyl that serves as a primer for reverse transcription of LINE-1 RNA by LIN...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng898

    authors： Morrish TA,Gilbert N,Myers JS,Vincent BJ,Stamato TD,Taccioli GE,Batzer MA,Moran JV

    更新日期：2002-06-01 00:00:00

  • A genetic link between cold responses and flowering time through FVE in Arabidopsis thaliana.

    abstract：:Cold induces expression of a number of genes that encode proteins that enhance tolerance to freezing temperatures in plants. A cis-acting element responsive to cold and drought, the C-repeat/dehydration-responsive element (C/DRE), was identified in the Arabidopsis thaliana stress-inducible genes RD29A and COR15a and f...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1298

    authors： Kim HJ,Hyun Y,Park JY,Park MJ,Park MK,Kim MD,Kim HJ,Lee MH,Moon J,Lee I,Kim J

    更新日期：2004-02-01 00:00:00

  • Probabilistic fine-mapping of transcriptome-wide association studies.

    abstract：:Transcriptome-wide association studies using predicted expression have identified thousands of genes whose locally regulated expression is associated with complex traits and diseases. In this work, we show that linkage disequilibrium induces significant gene-trait associations at non-causal genes as a function of the ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-019-0367-1

    authors： Mancuso N,Freund MK,Johnson R,Shi H,Kichaev G,Gusev A,Pasaniuc B

    更新日期：2019-04-01 00:00:00

  • MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM.

    abstract：:MASA syndrome is a recessive X-linked disorder characterized by mental retardation, adducted thumbs, shuffling gait, aphasia and, in some cases, hydrocephalus. Since it has been shown that X-linked hydrocephalus can be caused by mutations in L1CAM, a neuronal cell adhesion molecule, we performed an L1CAM mutation anal...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0794-408

    authors： Vits L,Van Camp G,Coucke P,Fransen E,De Boulle K,Reyniers E,Korn B,Poustka A,Wilson G,Schrander-Stumpel C

    更新日期：1994-07-01 00:00:00

  • Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

    abstract：:We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involve...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0223-8

    authors： Lilue J,Doran AG,Fiddes IT,Abrudan M,Armstrong J,Bennett R,Chow W,Collins J,Collins S,Czechanski A,Danecek P,Diekhans M,Dolle DD,Dunn M,Durbin R,Earl D,Ferguson-Smith A,Flicek P,Flint J,Frankish A,Fu B,Gerstein

    更新日期：2018-11-01 00:00:00

  • Enabling direct fate conversion with network biology.

    abstract：:Current efforts in cellular disease modeling and regenerative medicine are limited by the paucity of cell types that can be generated in the laboratory. A new study introduces a computational framework, Mogrify, that uses network biology to predict combinations of transcription factors necessary for direct conversion ...

    journal_title：Nature genetics

    pub_type： 评论,新闻

    doi：10.1038/ng.3516

    authors： Cahan P

    更新日期：2016-03-01 00:00:00

  • Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets.

    abstract：:Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3538

    authors： Zhu Z,Zhang F,Hu H,Bakshi A,Robinson MR,Powell JE,Montgomery GW,Goddard ME,Wray NR,Visscher PM,Yang J

    更新日期：2016-05-01 00:00:00

  • Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.

    abstract：:To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CH...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3943

    authors： Zhao W,Rasheed A,Tikkanen E,Lee JJ,Butterworth AS,Howson JMM,Assimes TL,Chowdhury R,Orho-Melander M,Damrauer S,Small A,Asma S,Imamura M,Yamauch T,Chambers JC,Chen P,Sapkota BR,Shah N,Jabeen S,Surendran P,Lu Y,Zh

    更新日期：2017-10-01 00:00:00

  • An evolutionary framework for measuring epigenomic information and estimating cell-type-specific fitness consequences.

    abstract：:Here we ask the question "How much information do epigenomic datasets provide about human genomic function?" We consider nine epigenomic features across 115 cell types and measure information about function as a reduction in entropy under a probabilistic evolutionary model fitted to human and nonhuman primate genomes....

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0300-z

    authors： Gulko B,Siepel A

    更新日期：2019-02-01 00:00:00

  • Publisher Correction: Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.

    abstract：:In the version of this article initially published, '+' and '-' labels were missing from the graph keys at the bottom of Fig. 8d. The error has been corrected in the HTML and PDF versions of the article. ...

    journal_title：Nature genetics

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41588-018-0341-3

    authors： Fanucchi S,Fok ET,Dalla E,Shibayama Y,Börner K,Chang EY,Stoychev S,Imakaev M,Grimm D,Wang KC,Li G,Sung WK,Mhlanga MM

    更新日期：2019-02-01 00:00:00

  • Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis.

    abstract：:It is now feasible to map disease genes by screening the genome for linkage disequilibrium between the disease and marker alleles. This report presents the first application of this approach for a previously unmapped locus. A gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by sear...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1294-380

    authors： Houwen RH,Baharloo S,Blankenship K,Raeymaekers P,Juyn J,Sandkuijl LA,Freimer NB

    更新日期：1994-12-01 00:00:00

  • Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate.

    abstract：:Pioneer transcription factors establish new cell-fate competence by triggering chromatin remodeling. However, many features of pioneer action, such as their kinetics and stability, remain poorly defined. Here, we show that Pax7, by opening a unique repertoire of enhancers, is necessary and sufficient for specification...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-017-0035-2

    authors： Mayran A,Khetchoumian K,Hariri F,Pastinen T,Gauthier Y,Balsalobre A,Drouin J

    更新日期：2018-02-01 00:00:00

  • Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin.

    abstract：:Friedreich's ataxia is due to loss of function mutations in the gene encoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected f...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0897-345

    authors： Koutnikova H,Campuzano V,Foury F,Dollé P,Cazzalini O,Koenig M

    更新日期：1997-08-01 00:00:00

  • Human artificial episomal chromosomes for cloning large DNA fragments in human cells.

    abstract：:We have developed a human artificial episomal chromosome (HAEC) system, based on the latent replication origin of the large herpes Epstein-Barr virus, for the propagation and stable maintenance of DNA as circular minichromosomes in human cells. Individual HAECs carried human genomic inserts ranging from 60-330 kb and ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0994-33

    authors： Sun TQ,Fenstermacher DA,Vos JM

    更新日期：1994-09-01 00:00:00

  • Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.

    abstract：:Wilson disease (WD) is an autosomal recessive disorder of copper transport which map to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD families ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1293-338

    authors： Petrukhin K,Fischer SG,Pirastu M,Tanzi RE,Chernov I,Devoto M,Brzustowicz LM,Cayanis E,Vitale E,Russo JJ

    更新日期：1993-12-01 00:00:00

  • Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

    abstract：:Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-α (ER-α, encoded by ESR1). Through a prospective clinical sequencing program for advanced cancers, we enrolled 11 patients with ER-positive metastatic breast cancer. Whole-exome and transcriptome analysis showed...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2823

    authors： Robinson DR,Wu YM,Vats P,Su F,Lonigro RJ,Cao X,Kalyana-Sundaram S,Wang R,Ning Y,Hodges L,Gursky A,Siddiqui J,Tomlins SA,Roychowdhury S,Pienta KJ,Kim SY,Roberts JS,Rae JM,Van Poznak CH,Hayes DF,Chugh R,Kunju LP,

    更新日期：2013-12-01 00:00:00