当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Fabry disease: twenty-three mutations including sense and antisense CpG alterations and identification of a deletional hot-spot in the alpha-galactosidase A gene.

Fabry disease: twenty-three mutations including sense and antisense CpG alterations and identification of a deletional hot-spot in the alpha-galactosidase A gene.

Abstract：

:Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A gene at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder variant Fabry phenotypes, and for precise carrier detection in Fabry families, the alpha-galactosidase A coding and flanking intronic sequences from 23 unrelated Fabry hemizygotes were analyzed. In patients with the classic phenotype, 16 new missense and nonsense mutations and four small exonic gene rearrangements were identified: C52S, C56F, E59K, L89R, R100K, R112H, L131P, A143P, G144V, C172Y, D244N, N272K, A288D, W81X, Q99X, Q157X, R301X, 25del1, 333del18, 358del6, and 1020del1. The R112H mutation at a CpG dinucleotide resulted in residual activity and a mild variant phenotype while the R112C lesion caused the classic disease manifestations, defining a genotype/phenotype correlation for sense and antisense mutations at the same CpG dinucleotide. In addition, two complex rearrangements, each involving two mutational events, occurred in classic hemizygotes. Both rearrangements resulted in missense mutations that did not change the reading frame. Notably, three of the deletions occurred within 11 codons in exon 2, thereby defining a 'hot-spot' for deletions. These studies revealed that most mutations in the alpha-galactosidase A gene causing Fabry disease were private, that codons 111-122 defined a deletion hot-spot, and that different substitutions of the same codon resulted in markedly different disease phenotypes.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Eng CM,Niehaus DJ,Enriquez AL,Burgert TS,Ludman MD,Desnick RJ

doi

10.1093/hmg/3.10.1795

subject

Has Abstract

pub_date

1994-10-01 00:00:00

pages

1795-9

issue

10

eissn

0964-6906

issn

1460-2083

journal_volume

3

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Impaired membrane traffic in defective ether lipid biosynthesis.

    abstract：:The first steps of ether lipid biosynthesis are exclusively localized to peroxisomes and hence some peroxisomal disorders are characterized by a severe deficiency of plasmalogens, the main ether lipids in humans. Here we report on gene defects of plasmalogen biosynthesis, chromosomal localization of the corresponding ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.2.127

    authors： Thai TP,Rodemer C,Jauch A,Hunziker A,Moser A,Gorgas K,Just WW

    更新日期：2001-01-15 00:00:00

  • Full-length dystrophin expression in half of the heart cells ameliorates beta-isoproterenol-induced cardiomyopathy in mdx mice.

    abstract：:Gene therapy holds great promise for curing Duchenne muscular dystrophy (DMD), the most common fatal inherited childhood muscle disease. Success of DMD gene therapy depends upon functional improvement in both skeletal and cardiac muscle. Numerous gene transfer studies have been performed to correct skeletal muscle pat...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh174

    authors： Yue Y,Skimming JW,Liu M,Strawn T,Duan D

    更新日期：2004-08-01 00:00:00

  • Biallelic expression of the IGF2 gene in human breast disease.

    abstract：:We examined the imprinting status of the insulin-like growth factor II gene (IGF2) in a series of 20 human breast disease samples to determine if disrupted imprinting (as evidenced by biallelic expression), was a demonstrable mechanism of altered gene expression. These samples included benign (n = 7) and malignant bre...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/5.8.1123

    authors： McCann AH,Miller N,O'Meara A,Pedersen I,Keogh K,Gorey T,Dervan PA

    更新日期：1996-08-01 00:00:00

  • Spinal muscular atrophy: mechanisms and therapeutic strategies.

    abstract：:Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder and a leading genetic cause of infantile mortality. SMA is caused by mutation or deletion of Survival Motor Neuron-1 (SMN1). The clinical features of the disease are caused by specific degeneration of alpha-motor neurons in the spinal c...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddq147

    authors： Lorson CL,Rindt H,Shababi M

    更新日期：2010-04-15 00:00:00

  • Inherited neurodegenerative diseases: the one-hit model of neurodegeneration.

    abstract：:The clinical manifestations of inherited neurodegenerative diseases are often delayed for periods from years to decades. This observation has led to the idea that, in these disorders, neurons die from cumulative damage. A critical prediction of the cumulative damage hypothesis is that the probability of neuronal death...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/10.20.2269

    authors： Clarke G,Lumsden CJ,McInnes RR

    更新日期：2001-10-01 00:00:00

  • Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy.

    abstract：:Proximal spinal muscular atrophy (SMA) is a common autosomal recessive childhood form of motor neuron disease. Previous studies have highlighted nerve- and muscle-specific events in SMA, including atrophy of muscle fibres and post-synaptic motor endplates, loss of lower motor neuron cell bodies and denervation of neur...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm367

    authors： Murray LM,Comley LH,Thomson D,Parkinson N,Talbot K,Gillingwater TH

    更新日期：2008-04-01 00:00:00

  • α-Synuclein levels modulate Huntington's disease in mice.

    abstract：:α-Synuclein and mutant huntingtin are the major constituents of the intracellular aggregates that characterize the pathology of Parkinson's disease (PD) and Huntington's disease (HD), respectively. α-Synuclein is likely to be a major contributor to PD, since overexpression of this protein resulting from genetic tripli...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr477

    authors： Corrochano S,Renna M,Carter S,Chrobot N,Kent R,Stewart M,Cooper J,Brown SD,Rubinsztein DC,Acevedo-Arozena A

    更新日期：2012-02-01 00:00:00

  • Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation.

    abstract：:To investigate the putative role of BRCA1, a gene involved in hereditary breast and ovarian cancer, in sporadic ovarian tumors among Japanese women, we examined 76 unselected primary ovarian cancers for mutations in the coding region of BRCA1 using the single-strand conformation polymorphism technique. Although no som...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.10.1953

    authors： Matsushima M,Kobayashi K,Emi M,Saito H,Saito J,Suzumori K,Nakamura Y

    更新日期：1995-10-01 00:00:00

  • An evolutionarily conserved germ cell-specific hnRNP is encoded by a retrotransposed gene.

    abstract：:The gene encoding heterogeneous ribonucleoprotein (hnRNP) G recently has been mapped to the X chromosome. All mammals have a Y chromosome-encoded homologue of HNRNP G called RBMY, which is implicated with a role in male fertility and is a candidate for the azoospermia factor gene. We have identified a new member of th...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.14.2117

    authors： Elliott DJ,Venables JP,Newton CS,Lawson D,Boyle S,Eperon IC,Cooke HJ

    更新日期：2000-09-01 00:00:00

  • Variegated yet non-random rod and cone photoreceptor disease patterns in RPGR-ORF15-associated retinal degeneration.

    abstract：:Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially tre...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw361

    authors： Charng J,Cideciyan AV,Jacobson SG,Sumaroka A,Schwartz SB,Swider M,Roman AJ,Sheplock R,Anand M,Peden MC,Khanna H,Heon E,Wright AF,Swaroop A

    更新日期：2016-12-15 00:00:00

  • Functional screening in Drosophila reveals the conserved role of REEP1 in promoting stress resistance and preventing the formation of Tau aggregates.

    abstract：:Pathological modifications in the microtubule-associated protein Tau is a common characteristic observed in different neurological diseases, suggesting that analogous metabolic pathways might be similarly affected during neurodegeneration. To identify these molecules and mechanisms, we utilized Drosophila models of hu...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu393

    authors： Appocher C,Klima R,Feiguin F

    更新日期：2014-12-20 00:00:00

  • Reduced protein turnover mediates functional deficits in transgenic mice expressing the 25 kDa C-terminal fragment of TDP-43.

    abstract：:Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) are two neurodegenerative disorders characterized by the accumulation of TDP-43. TDP-43 is proteolitically cleaved to generate two major C-terminal fragments of 35 and 25 kDa. The latter, known as TDP-25, is a consistent feature of FT...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv193

    authors： Caccamo A,Shaw DM,Guarino F,Messina A,Walker AW,Oddo S

    更新日期：2015-08-15 00:00:00

  • Parkinson's disease-linked DNAJC13 mutation aggravates alpha-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.

    abstract：:Mutations in DNAJC13 gene have been linked to familial form of Parkinson's disease (PD) with Lewy pathology. DNAJC13 is an endosome-related protein and believed to regulate endosomal membrane trafficking. However, the mechanistic link between DNAJC13 mutation and α-synuclein (αSYN) pathology toward neurodegeneration r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy003

    authors： Yoshida S,Hasegawa T,Suzuki M,Sugeno N,Kobayashi J,Ueyama M,Fukuda M,Ido-Fujibayashi A,Sekiguchi K,Ezura M,Kikuchi A,Baba T,Takeda A,Mochizuki H,Nagai Y,Aoki M

    更新日期：2018-03-01 00:00:00

  • Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli.

    abstract：:Nicotine is thought to act on brain monoamine systems that normally mediate diverse motivational behaviors. How monoamine-related genes contribute to behavioral traits (e.g. responses to novel stimuli) comorbid with the susceptibility to nicotine addiction is still poorly understood. We examined the impact of constitu...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl206

    authors： Agatsuma S,Lee M,Zhu H,Chen K,Shih JC,Seif I,Hiroi N

    更新日期：2006-09-15 00:00:00

  • Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.

    abstract：:We have previously developed a functional assay in yeast for the copper transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant ATP7B proteins revealed that several were able to completely, or nearly completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was disrupted, ind...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.13.1927

    authors： Forbes JR,Cox DW

    更新日期：2000-08-12 00:00:00

  • Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up.

    abstract：:Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc....

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds099

    authors： Martin JE,Broen JC,Carmona FD,Teruel M,Simeon CP,Vonk MC,van 't Slot R,Rodriguez-Rodriguez L,Vicente E,Fonollosa V,Ortego-Centeno N,González-Gay MA,García-Hernández FJ,de la Peña PG,Carreira P,Spanish Scleroderma Group.,V

    更新日期：2012-06-15 00:00:00

  • The Old World monkey DAZ (Deleted in AZoospermia) gene yields insights into the evolution of the DAZ gene cluster on the human Y chromosome.

    abstract：:The DAZ gene cluster on the human Y chromosome is a candidate for the Azoospermia Factor (AZFc). According to the current evolutionary model, the DAZ cluster derived from the autosomal homolog DAZL1 through duplications and rearrangements and is confined to Old World monkeys, apes and humans. To study functional and e...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/8.11.2017

    authors： Gromoll J,Weinbauer GF,Skaletsky H,Schlatt S,Rocchietti-March M,Page DC,Nieschlag E

    更新日期：1999-10-01 00:00:00

  • New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11.

    abstract：:Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in ∼100 genes. Although recent advances in next-generation sequencing have aided in the discovery of novel RP genes, a number of the underlying contributing genes a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu291

    authors： Xie YA,Lee W,Cai C,Gambin T,Nõupuu K,Sujirakul T,Ayuso C,Jhangiani S,Muzny D,Boerwinkle E,Gibbs R,Greenstein VC,Lupski JR,Tsang SH,Allikmets R

    更新日期：2014-11-01 00:00:00

  • Loss of LDAH associated with prostate cancer and hearing loss.

    abstract：:Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the unde...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy310

    authors： Currall BB,Chen M,Sallari RC,Cotter M,Wong KE,Robertson NG,Penney KL,Lunardi A,Reschke M,Hickox AE,Yin Y,Wong GT,Fung J,Brown KK,Williamson RE,Sinnott-Armstrong NA,Kammin T,Ivanov A,Zepeda-Mendoza CJ,Shen J,Quade

    更新日期：2018-12-15 00:00:00

  • Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila.

    abstract：:Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought to confer toxic properties on the disease proteins through alt...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg144

    authors： Nagai Y,Fujikake N,Ohno K,Higashiyama H,Popiel HA,Rahadian J,Yamaguchi M,Strittmatter WJ,Burke JR,Toda T

    更新日期：2003-06-01 00:00:00

  • Allelic recombination and de novo deletions in sperm in the human beta-globin gene region.

    abstract：:Meiotic recombination is of fundamental importance in creating haplotype diversity in the human genome and has the potential to cause genomic rearrangements by ectopic recombination between repeat sequences and through other changes triggered by recombination-initiating events. However, the relationship between alleli...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl025

    authors： Holloway K,Lawson VE,Jeffreys AJ

    更新日期：2006-04-01 00:00:00

  • The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration.

    abstract：:Parkinson's disease (PD) is a severe neurological disorder, characterized by the progressive degeneration of the dopaminergic nigrostriatal pathway and the presence of Lewy bodies (LBs). The discovery of genes responsible for familial forms of the disease has provided insights into its pathogenesis. Mutations in the p...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg159

    authors： Corti O,Hampe C,Koutnikova H,Darios F,Jacquier S,Prigent A,Robinson JC,Pradier L,Ruberg M,Mirande M,Hirsch E,Rooney T,Fournier A,Brice A

    更新日期：2003-06-15 00:00:00

  • Deleting nebulin's C-terminus reveals its importance to sarcomeric structure and function and is sufficient to invoke nemaline myopathy.

    abstract：:Nebulin is a large skeletal muscle protein wound around the thin filaments, with its C-terminus embedded within the Z-disk and its N-terminus extending out toward the thin filament pointed end. While nebulin's C-terminus has been implicated in both sarcomeric structure and function as well as the development of nemali...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz016

    authors： Li F,Barton ER,Granzier H

    更新日期：2019-05-15 00:00:00

  • Chylomicronemia mutations yield new insights into interactions between lipoprotein lipase and GPIHBP1.

    abstract：:Lipoprotein lipase (LPL) is a 448-amino-acid head-to-tail dimeric enzyme that hydrolyzes triglycerides within capillaries. LPL is secreted by parenchymal cells into the interstitial spaces; it then binds to GPIHBP1 (glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1) on the basolateral fa...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds127

    authors： Gin P,Goulbourne CN,Adeyo O,Beigneux AP,Davies BS,Tat S,Voss CV,Bensadoun A,Fong LG,Young SG

    更新日期：2012-07-01 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

    doi：10.1093/hmg/ddn091

    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

  • Comparison of spinocerebellar ataxia type 3 mouse models identifies early gain-of-function, cell-autonomous transcriptional changes in oligodendrocytes.

    abstract：:Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3 gene. This expansion leads to misfolding and aggregation of mutant ataxin-3 (ATXN3) and degeneration of select brain regions. A key unanswered question in SCA3 and other polyglutami...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx224

    authors： Ramani B,Panwar B,Moore LR,Wang B,Huang R,Guan Y,Paulson HL

    更新日期：2017-09-01 00:00:00

  • Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability.

    abstract：:The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw383

    authors： Breuss MW,Nguyen T,Srivatsan A,Leca I,Tian G,Fritz T,Hansen AH,Musaev D,McEvoy-Venneri J,James KN,Rosti RO,Scott E,Tan U,Kolodner RD,Cowan NJ,Keays DA,Gleeson JG

    更新日期：2017-01-15 00:00:00

  • Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease.

    abstract：:Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv358

    authors： Cha MY,Cho HJ,Kim C,Jung YO,Kang MJ,Murray ME,Hong HS,Choi YJ,Choi H,Kim DK,Choi H,Kim J,Dickson DW,Song HK,Cho JW,Yi EC,Kim J,Jin SM,Mook-Jung I

    更新日期：2015-11-15 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

    doi：10.1093/hmg/3.1.99

    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

  • Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma.

    abstract：:Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contri...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr593

    authors： Bebek G,Bennett KL,Funchain P,Campbell R,Seth R,Scharpf J,Burkey B,Eng C

    更新日期：2012-04-01 00:00:00