当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

Abstract：

:A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

von Ameln S,Wang G,Boulouiz R,Rutherford MA,Smith GM,Li Y,Pogoda HM,Nürnberg G,Stiller B,Volk AE,Borck G,Hong JS,Goodyear RJ,Abidi O,Nürnberg P,Hofmann K,Richardson GP,Hammerschmidt M,Moser T,Wollnik B,Koehler CM

doi

10.1016/j.ajhg.2012.09.002

subject

Has Abstract

pub_date

2012-11-02 00:00:00

pages

919-27

issue

5

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(12)00476-4

journal_volume

91

pub_type

杂志文章

相关文献

AMERICAN JOURNAL OF HUMAN GENETICS文献大全
  • A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2.

    abstract：:Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/377156

    authors： Abalkhail H,Mitchell J,Habgood J,Orrell R,de Belleroche J

    更新日期：2003-08-01 00:00:00

  • Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema.

    abstract：:Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modul...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302729

    authors： Yamada N,Yamaya M,Okinaga S,Nakayama K,Sekizawa K,Shibahara S,Sasaki H

    更新日期：2000-01-01 00:00:00

  • Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.

    abstract：:We describe a maternally transmitted genomic-imprinting syndrome of mental retardation, hypotonia, and unique dysmorphism with elongated face. We mapped the disease-associated locus to approximately 7.27 Mb on chromosome 8q24 and demonstrated that the disease is caused by a missense mutation in the maternal copy of KC...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2008.07.010

    authors： Barel O,Shalev SA,Ofir R,Cohen A,Zlotogora J,Shorer Z,Mazor G,Finer G,Khateeb S,Zilberberg N,Birk OS

    更新日期：2008-08-01 00:00:00

  • Mental retardation in heterozygotes for the fragile-X mutation: evidence in favor of an X inactivation-dependent effect.

    abstract：:The still debated question of whether the expression of mental retardation in heterozygous carriers of the Martin-Bell syndrome is influenced by X inactivation has been investigated in a group of phase-known double heterozygotes for the FRA-X mutant and the G6PD Mediterranean variant. In these individuals, the number ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Rocchi M,Archidiacono N,Rinaldi A,Filippi G,Bartolucci G,Fancello GS,Siniscalco M

    更新日期：1990-04-01 00:00:00

  • Study of two cases of ring 13 chromosome using high-resolution banding.

    abstract：:The chromosomes of two patients with ring 13 (r13) were studied using high-resolution RBG banding of prometaphase cells. The rings of the two patients differ slightly in breakpoints. Cell with multiple single, double-sized rings, quadruple-sized rings, rod- and ring-shaped fragments, and fragments showing varied state...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Jones IM,Palmer CG,Weaver DD,Hodes ME

    更新日期：1981-03-01 00:00:00

  • Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.

    abstract：:Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive genetic disease caused by a deficiency of the lysosomal glycosidase alpha-L-iduronidase. Hurler (severe), Scheie (mild), and Hurler/Scheie (intermediate) syndromes are clinical subtypes of MPS-I, but it is difficult to distinguish between these subtypes by...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Scott HS,Litjens T,Nelson PV,Thompson PR,Brooks DA,Hopwood JJ,Morris CP

    更新日期：1993-11-01 00:00:00

  • Pre-Caucasoid and Caucasoid genetic features of the Indian population, revealed by mtDNA polymorphisms.

    abstract：:About 70 individuals from Punjab were examined for some mtDNA polymorphisms, namely, the RFLPs of the six classical enzymes (HpaI, BamHI, HaeII, MspI, AvaII, and Hin-cII) and for the sites AluI(7,025), DdeI(10,394), and AluI(10,397). The AluI(7,025) polymorphic site was also investigated in 96 Indians from Uttar Prade...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Passarino G,Semino O,Bernini LF,Santachiara-Benerecetti AS

    更新日期：1996-10-01 00:00:00

  • Genome-wide insights into the patterns and determinants of fine-scale population structure in humans.

    abstract：:Studying genomic patterns of human population structure provides important insights into human evolutionary history and the relationship among populations, and it has significant practical implications for disease-gene mapping. Here we describe a principal component (PC)-based approach to studying intracontinental pop...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2009.04.015

    authors： Biswas S,Scheinfeldt LB,Akey JM

    更新日期：2009-05-01 00:00:00

  • Teaching human genetics in biochemistry by computer literature searching.

    abstract：:We describe a new user-intense-learning experience that incorporates the teaching of clinical and research applications of human genetics in biochemistry while training first-year medical students to develop skills in computer access to the literature. Human genetics was incorporated into the biochemistry curriculum b...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Proud VK,Schmidt FJ,Johnson ED,Mitchell JA

    更新日期：1989-04-01 00:00:00

  • Evidence for the close linkage between lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase D.

    abstract：:The genetic linkage of the loci for lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase (ESD) were examined by two-dimensional gel electrophoresis using blood from four informative families. No recombinants were observed in the four families totaling 17 children, giving a summed lod scor...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Kondo I,Hamaguchi H

    更新日期：1985-11-01 00:00:00

  • Distinct mutations in the receptor tyrosine kinase gene ROR2 cause brachydactyly type B.

    abstract：:Brachydactyly type B (BDB) is an autosomal dominant skeletal disorder characterized by hypoplasia/aplasia of distal phalanges and nails. Recently, heterozygous mutations of the orphan receptor tyrosine kinase (TK) ROR2, located within a distinct segment directly after the TK domain, have been shown to be responsible f...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/303084

    authors： Schwabe GC,Tinschert S,Buschow C,Meinecke P,Wolff G,Gillessen-Kaesbach G,Oldridge M,Wilkie AO,Kömec R,Mundlos S

    更新日期：2000-10-01 00:00:00

  • Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.

    abstract：:Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/301713

    authors： Briggs MD,Mortier GR,Cole WG,King LM,Golik SS,Bonaventure J,Nuytinck L,De Paepe A,Leroy JG,Biesecker L,Lipson M,Wilcox WR,Lachman RS,Rimoin DL,Knowlton RG,Cohn DH

    更新日期：1998-02-01 00:00:00

  • Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population.

    abstract：:Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have no...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2012.02.011

    authors： Srour M,Schwartzentruber J,Hamdan FF,Ospina LH,Patry L,Labuda D,Massicotte C,Dobrzeniecka S,Capo-Chichi JM,Papillon-Cavanagh S,Samuels ME,Boycott KM,Shevell MI,Laframboise R,Désilets V,FORGE Canada Consortium.,Maranda B,

    更新日期：2012-04-06 00:00:00

  • Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene.

    abstract：:The human SNRPN (small nuclear ribonucleoprotein polypeptide N) gene is one of a gene family that encode proteins involved in pre-mRNA splicing and maps to the smallest deletion region involved in the Prader-Willi syndrome (PWS) within chromosome 15q11-q13. Paternal only expression of SNRPN has previously been demonst...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Glenn CC,Saitoh S,Jong MT,Filbrandt MM,Surti U,Driscoll DJ,Nicholls RD

    更新日期：1996-02-01 00:00:00

  • Gonadoblastoma: molecular definition of the susceptibility region on the Y chromosome.

    abstract：:Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was sublocalized to a small region near the centromere of the Y chromosome. We estimate the size of the GBY ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Tsuchiya K,Reijo R,Page DC,Disteche CM

    更新日期：1995-12-01 00:00:00

  • HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans.

    abstract：:The heterogeneous nuclear ribonucleoprotein (HNRNP) genes code for a set of RNA-binding proteins that function primarily in the spliceosome C complex. Pathogenic variants in these genes can drive neurodegeneration, through a mechanism involving excessive stress-granule formation, or developmental defects, through mech...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2019.03.024

    authors： Duijkers FA,McDonald A,Janssens GE,Lezzerini M,Jongejan A,van Koningsbruggen S,Leeuwenburgh-Pronk WG,Wlodarski MW,Moutton S,Tran-Mau-Them F,Thauvin-Robinet C,Faivre L,Monaghan KG,Smol T,Boute-Benejean O,Ladda RL,Sell SL,

    更新日期：2019-06-06 00:00:00

  • Meta-analysis of gene-level associations for rare variants based on single-variant statistics.

    abstract：:Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are perf...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,meta分析

    doi：10.1016/j.ajhg.2013.06.011

    authors： Hu YJ,Berndt SI,Gustafsson S,Ganna A,Genetic Investigation of ANthropometric Traits (GIANT) Consortium.,Hirschhorn J,North KE,Ingelsson E,Lin DY

    更新日期：2013-08-08 00:00:00

  • Wilson disease in Iceland: a clinical and genetic study.

    abstract：:A survey of Wilson disease in Iceland has revealed two large kindreds with affected individuals. We have carried out studies of haplotypes of dinucleotide repeat polymorphisms (CA repeats) flanking the Wilson disease gene. The same mutation, a 7-bp deletion, is present in both families, and the clinical features are s...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Thomas GR,Jensson O,Gudmundsson G,Thorsteinsson L,Cox DW

    更新日期：1995-05-01 00:00:00

  • Combined use of biallelic and microsatellite Y-chromosome polymorphisms to infer affinities among African populations.

    abstract：:To define Y-chromosome haplotypes, we studied seven biallelic polymorphic sites. We combined data with those from four dinucleotide-repeat polymorphisms, to establish Y-chromosome compound superhaplotypes. Eight biallelic haplotypes that matched the dendrogram proposed by other investigators were identified in 762 Y c...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302538

    authors： Scozzari R,Cruciani F,Santolamazza P,Malaspina P,Torroni A,Sellitto D,Arredi B,Destro-Bisol G,De Stefano G,Rickards O,Martinez-Labarga C,Modiano D,Biondi G,Moral P,Olckers A,Wallace DC,Novelletto A

    更新日期：1999-09-01 00:00:00

  • Recent developments in genomewide association scans: a workshop summary and review.

    abstract：:With the imminent availability of ultra-high-volume genotyping platforms (on the order of 100,000-1,000,000 genotypes per sample) at a manageable cost, there is growing interest in the possibility of conducting genomewide association studies for a variety of diseases but, so far, little consensus on methods to design ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,评审

    doi：10.1086/432962

    authors： Thomas DC,Haile RW,Duggan D

    更新日期：2005-09-01 00:00:00

  • On the probabilities of identity states in permutable populations.

    abstract：:Génin and Clerget-Darpoux recently discussed the derivation of the probabilities of identity states for populations in which there was some degree of kinship, primarily to allow the extension of the classical affected-sib-pair method to such populations. It is argued here that their derivation makes certain assumption...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/301743

    authors： Cannings C

    更新日期：1998-03-01 00:00:00

  • Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.

    abstract：:We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,meta分析

    doi：10.1016/j.ajhg.2016.07.012

    authors： Mahajan A,Rodan AR,Le TH,Gaulton KJ,Haessler J,Stilp AM,Kamatani Y,Zhu G,Sofer T,Puri S,Schellinger JN,Chu PL,Cechova S,van Zuydam N,SUMMIT Consortium.,BioBank Japan Project.,Arnlov J,Flessner MF,Giedraitis V,Heath

    更新日期：2016-09-01 00:00:00

  • A highly polymorphic locus in human DNA revealed by probes from cosmid 1-5 maps to chromosome 2q35----37.

    abstract：:The highly polymorphic locus D2S3 is revealed by three single-copy probes from cosmid C1-5. These probes, 1-30, 1-32, and 2-96, collectively reveal seven restriction fragment length polymorphisms. Fifty-three of 56 unrelated individuals (93%) were heterozygous at one or more of the seven loci, making the compound locu...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Litt M,Bruns GA,Sheehy R,Magenis RE

    更新日期：1986-03-01 00:00:00

  • The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier males.

    abstract：:Craniofrontonasal syndrome (CFNS) is an X-linked disorder that exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis, and additional minor malformations, but males are usually mildly affected with hypertelorism only. Despite this, males appe...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/504440

    authors： Twigg SR,Matsumoto K,Kidd AM,Goriely A,Taylor IB,Fisher RB,Hoogeboom AJ,Mathijssen IM,Lourenco MT,Morton JE,Sweeney E,Wilson LC,Brunner HG,Mulliken JB,Wall SA,Wilkie AO

    更新日期：2006-06-01 00:00:00

  • Cystic fibrosis carrier population screening in the primary care setting.

    abstract：:To determine the receptivity of prenatal care providers and their patients to carrier testing for cystic fibrosis (CF), we offered free carrier screening, followed by genetic counseling of carriers, to all prenatal care providers in Rochester, NY, for all their female patients of reproductive age, pregnant or not. Of ...

    journal_title：American journal of human genetics

    pub_type： 临床试验,杂志文章

    doi：

    authors： Loader S,Caldwell P,Kozyra A,Levenkron JC,Boehm CD,Kazazian HH Jr,Rowley PT

    更新日期：1996-07-01 00:00:00

  • Enzymological and mutational analysis of a complex primary hyperoxaluria type 1 phenotype involving alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation.

    abstract：:Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is character...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Danpure CJ,Purdue PE,Fryer P,Griffiths S,Allsop J,Lumb MJ,Guttridge KM,Jennings PR,Scheinman JI,Mauer SM

    更新日期：1993-08-01 00:00:00

  • Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies.

    abstract：:Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, loca...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Hecht JT,Hogue D,Wang Y,Blanton SH,Wagner M,Strong LC,Raskind W,Hansen MF,Wells D

    更新日期：1997-01-01 00:00:00

  • Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci.

    abstract：:Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonpa...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/319509

    authors： Laval SH,Timms A,Edwards S,Bradbury L,Brophy S,Milicic A,Rubin L,Siminovitch KA,Weeks DE,Calin A,Wordsworth BP,Brown MA

    更新日期：2001-04-01 00:00:00

  • Linkage of Paget disease of bone to a novel region on human chromosome 18q23.

    abstract：:Paget disease of bone (PDB) is characterized by increased osteoclast activity and localized abnormal bone remodeling. PDB has a significant genetic component, with evidence of linkage to chromosomes 6p21.3 (PDB1) and 18q21-22 (PDB2) in some pedigrees. There is evidence of genetic heterogeneity, with other pedigrees sh...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/338658

    authors： Good DA,Busfield F,Fletcher BH,Duffy DL,Kesting JB,Andersen J,Shaw JT

    更新日期：2002-02-01 00:00:00

  • Origin of the triosephosphate isomerase isozymes in humans: genetic evidence for the expression of a single structural locus.

    abstract：:A genetic approach is used to ascertain that a single structural locus for triosephosphate isomerase (TPI) (E.C.5.3.1.1.) is expressed in rapidly dividing human lymphoblasts. This approach is made possible through the identification of a rare electrophoretic variant of human TPI. The variant phenotype is expressed by ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Decker RS,Mohrenweiser HW

    更新日期：1981-09-01 00:00:00