Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.

Abstract:

:Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Morante-Redolat JM,Gorostidi-Pagola A,Piquer-Sirerol S,Sáenz A,Poza JJ,Galán J,Gesk S,Sarafidou T,Mautner VF,Binelli S,Staub E,Hinzmann B,French L,Prud'homme JF,Passarelli D,Scannapieco P,Tassinari CA,Avanzini G,Martí

doi

10.1093/hmg/11.9.1119

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

1119-28

issue

9

eissn

0964-6906

issn

1460-2083

journal_volume

11

pub_type

杂志文章
  • Polymorphism in the activity of human crossover hotspots independent of local DNA sequence variation.

    abstract::Meiotic crossovers in the human genome cluster into highly localized hotspots identifiable indirectly from patterns of DNA diversity and directly by high-resolution sperm typing. Little is known about factors that control hotspot activity and the apparently rapid turnover of hotspots during recent evolution. Clues can...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl063

    authors: Neumann R,Jeffreys AJ

    更新日期:2006-05-01 00:00:00

  • Mutant huntingtin's interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington's disease.

    abstract::The purpose of this study was to investigate the link between mutant huntingtin (Htt) and neuronal damage in relation to mitochondria in Huntington's disease (HD). In an earlier study, we determined the relationship between mutant Htt and mitochondrial dynamics/synaptic viability in HD patients. We found mitochondrial...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr475

    authors: Shirendeb UP,Calkins MJ,Manczak M,Anekonda V,Dufour B,McBride JL,Mao P,Reddy PH

    更新日期:2012-01-15 00:00:00

  • Subcellular localization and RNAs determine FUS architecture in different cellular compartments.

    abstract::Mutations in Fused in sarcoma (FUS) gene cause a subset of familial amyotrophic lateral sclerosis (ALS), a fatal motor neuron degenerative disease. Wild-type FUS is largely localized in the nucleus, but mutant FUS accumulates in the cytoplasm and forms inclusions. It is unclear whether FUS depletion from the nucleus o...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddv239

    authors: Yang L,Zhang J,Kamelgarn M,Niu C,Gal J,Gong W,Zhu H

    更新日期:2015-09-15 00:00:00

  • Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease.

    abstract::Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddn106

    authors: Alves S,Régulier E,Nascimento-Ferreira I,Hassig R,Dufour N,Koeppen A,Carvalho AL,Simões S,de Lima MC,Brouillet E,Gould VC,Déglon N,de Almeida LP

    更新日期:2008-07-15 00:00:00

  • Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse.

    abstract::The quakingviable mouse (qkv) is a spontaneous recessive mouse mutant with a deletion of approximately 1.1 Mb in the proximal region of chromosome 17. The deletion affects the expression of three genes; quaking (Qk), Parkin-coregulated gene (Pacrg) and parkin (Park2). The resulting phenotype, which includes dysmyelina...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq031

    authors: Wilson GR,Wang HX,Egan GF,Robinson PJ,Delatycki MB,O'Bryan MK,Lockhart PJ

    更新日期:2010-04-15 00:00:00

  • Ataxia-telangiectasia: founder effect among north African Jews.

    abstract::The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition. A-T carriers were reported to be moderately cancer-prone. A wide variety of A-T mutations, most of which are unique to single families, wer...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/5.12.2033

    authors: Gilad S,Bar-Shira A,Harnik R,Shkedy D,Ziv Y,Khosravi R,Brown K,Vanagaite L,Xu G,Frydman M,Lavin MF,Hill D,Tagle DA,Shiloh Y

    更新日期:1996-12-01 00:00:00

  • The biological impact of blood pressure-associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.

    abstract::Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association stu...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddx375

    authors: Ren M,Ng FL,Warren HR,Witkowska K,Baron M,Jia Z,Cabrera C,Zhang R,Mifsud B,Munroe PB,Xiao Q,Townsend-Nicholson A,Hobbs AJ,Ye S,Caulfield MJ

    更新日期:2018-01-01 00:00:00

  • Molecular modeling of retinoschisin with functional analysis of pathogenic mutations from human X-linked retinoschisis.

    abstract::Gene mutations that encode retinoschisin (RS1) cause X-linked retinoschisis (XLRS), a form of juvenile macular and retinal degeneration that affects males. RS1 is an adhesive protein which is proposed to preserve the structural and functional integrity of the retina, but there is very little evidence of the mechanism ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq006

    authors: Sergeev YV,Caruso RC,Meltzer MR,Smaoui N,MacDonald IM,Sieving PA

    更新日期:2010-04-01 00:00:00

  • A mouse model of Angelman syndrome imprinting defects.

    abstract::Angelman syndrome, Prader-Will syndrome and Dup15q syndrome map to a cluster of imprinted genes located at 15q11-q13. Imprinting at this domain is regulated by an imprinting control region consisting of two distinct elements, the Angelman syndrome imprinting center (AS-IC) and the Prader-Willi syndrome imprinting cent...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddy345

    authors: Lewis MW,Vargas-Franco D,Morse DA,Resnick JL

    更新日期:2019-01-15 00:00:00

  • PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains.

    abstract::Huntington's disease (HD) is caused by a pathological expansion of a CAG repeat in the first exon of the gene coding for huntingtin, resulting in an abnormally long polyglutamine stretch. Despite its widespread expression, mutant huntingtin leads to selective neuronal loss in the striatum and cortex. Here we report th...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/11.21.2547

    authors: Modregger J,DiProspero NA,Charles V,Tagle DA,Plomann M

    更新日期:2002-10-01 00:00:00

  • Tumoral EPAS1 (HIF2A) mutations explain sporadic pheochromocytoma and paraganglioma in the absence of erythrocytosis.

    abstract::Pheochromocytomas (PCCs) and paragangliomas (PGLs) are chromaffin-cell tumors that arise from the adrenal medulla and extra-adrenal paraganglia, respectively. The dysfunction of genes involved in the cellular response to hypoxia, such as VHL, EGL nine homolog 1, and the succinate dehydrogenase (SDH) genes, leads to a ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddt069

    authors: Comino-Méndez I,de Cubas AA,Bernal C,Álvarez-Escolá C,Sánchez-Malo C,Ramírez-Tortosa CL,Pedrinaci S,Rapizzi E,Ercolino T,Bernini G,Bacca A,Letón R,Pita G,Alonso MR,Leandro-García LJ,Gómez-Graña A,Inglada-Pérez L,Manciko

    更新日期:2013-06-01 00:00:00

  • The molecular pathogenesis of migraine: new developments and opportunities.

    abstract::Migraine is a prevalent, debilitating and costly disorder with an ongoing unmet medical need. Human genetic studies have provided considerable insights into the molecular underpinnings of this complex brain disorder. Classical linkage studies have revealed the causes of familial hemiplegic migraine, while more recentl...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审

    doi:10.1093/hmg/ddt364

    authors: Zameel Cader M

    更新日期:2013-10-15 00:00:00

  • Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations.

    abstract::We describe and functionally characterize six mutations of the acetylcholine receptor (AChR) epsilon subunit gene in three congenital myasthenic syndrome patients. Endplate studies demonstrated severe endplate AChR deficiency, dispersed endplate regions and well preserved junctional folds in all three patients. Electr...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/6.5.753

    authors: Ohno K,Quiram PA,Milone M,Wang HL,Harper MC,Pruitt JN 2nd,Brengman JM,Pao L,Fischbeck KH,Crawford TO,Sine SM,Engel AG

    更新日期:1997-05-01 00:00:00

  • The survival gene MED4 explains low penetrance retinoblastoma in patients with large RB1 deletion.

    abstract::Retinoblastoma is a non-hereditary as well as an inherited pediatric tumor of the developing retina resulting from the inactivation of both copies of the RB1 tumor suppressor gene. Familial retinoblastoma is a highly penetrant genetic disease that usually develops by carrying germline mutations that inactivate one all...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddu245

    authors: Dehainault C,Garancher A,Castéra L,Cassoux N,Aerts I,Doz F,Desjardins L,Lumbroso L,Montes de Oca R,Almouzni G,Stoppa-Lyonnet D,Pouponnot C,Gauthier-Villars M,Houdayer C

    更新日期:2014-10-01 00:00:00

  • Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice.

    abstract::Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of A beta deposits. In the present study, we asked whether elevating the levels of Apo E can, in a dominant fashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via the mouse prion prote...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/10.22.2525

    authors: Lesuisse C,Xu G,Anderson J,Wong M,Jankowsky J,Holtz G,Gonzalez V,Wong PC,Price DL,Tang F,Wagner S,Borchelt DR

    更新日期:2001-10-15 00:00:00

  • Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis.

    abstract::Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gai...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddg352

    authors: Kennedy L,Evans E,Chen CM,Craven L,Detloff PJ,Ennis M,Shelbourne PF

    更新日期:2003-12-15 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

    doi:10.1093/hmg/8.7.1245

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

    更新日期:1999-07-01 00:00:00

  • Molecular diagnosis of homozygous myotonic dystrophy in two asymptomatic sisters.

    abstract::The genetic defect underlying myotonic dystrophy (DM) has been identified as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic counselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/2.6.711

    authors: Cobo A,Martinez JM,Martorell L,Baiget M,Johnson K

    更新日期:1993-06-01 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

  • Mitochondrial DNA segregation in hematopoietic lineages does not depend on MHC presentation of mitochondrially encoded peptides.

    abstract::Mutations in mitochondrial DNA (mtDNA) are associated with a broad spectrum of clinical disorders. The segregation pattern of pathogenic mtDNAs is an important determinant of both the onset and the severity of the disease phenotype, but the mechanisms controlling mtDNA segregation remain poorly understood. To investig...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddi293

    authors: Battersby BJ,Redpath ME,Shoubridge EA

    更新日期:2005-09-01 00:00:00

  • Expression of the von Hippel-Lindau-binding protein-1 (Vbp1) in fetal and adult mouse tissues.

    abstract::The von Hippel-Lindau (VHL) tumour suppressorgene product is believed to be involved in the down-regulation of transcriptional elongation by preventing the association of elongin B and C with the catalytic subunit elongin A. Alterations in the human VHL gene lead to VHL disease which is associated with various rare ne...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/8.2.229

    authors: Hemberger M,Himmelbauer H,Neumann HP,Plate KH,Schwarzkopf G,Fundele R

    更新日期:1999-02-01 00:00:00

  • Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1.

    abstract::The members of the huntingtin-interacting protein-1 (HIP1) family, HIP1 and HIP1-related (HIP1r), are multi-domain proteins that interact with inositol lipids, clathrin and actin. HIP1 is over-expressed in a variety of cancers and both HIP1 and HIP1r prolong the half-life of multiple growth factor receptors. To better...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddm076

    authors: Bradley SV,Hyun TS,Oravecz-Wilson KI,Li L,Waldorff EI,Ermilov AN,Goldstein SA,Zhang CX,Drubin DG,Varela K,Parlow A,Dlugosz AA,Ross TS

    更新日期:2007-06-01 00:00:00

  • Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.

    abstract::Functional and genomic approaches can be integrated to screen efficiently for pathogenic alleles in founder populations. We applied such approaches to analysis of the cancer-associated cell cycle regulator CHEK2 in the Ashkenazi Jewish population. We first identified two extended haplotypes at CHEK2 that co-segregated...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddi052

    authors: Shaag A,Walsh T,Renbaum P,Kirchhoff T,Nafa K,Shiovitz S,Mandell JB,Welcsh P,Lee MK,Ellis N,Offit K,Levy-Lahad E,King MC

    更新日期:2005-02-15 00:00:00

  • Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats.

    abstract::Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains unknown. To determ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddh147

    authors: Tian XL,Pinto YM,Costerousse O,Franz WM,Lippoldt A,Hoffmann S,Unger T,Paul M

    更新日期:2004-07-15 00:00:00

  • Signatures of adaptive evolution within human non-coding sequence.

    abstract::The human genome is often portrayed as consisting of three sequence types, each distinguished by their mode of evolution. Purifying selection is estimated to act on 2.5-5.0% of the genome, whereas virtually all remaining sequence is considered to have evolved neutrally and to be devoid of functionality. The third mode...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审

    doi:10.1093/hmg/ddl182

    authors: Ponting CP,Lunter G

    更新日期:2006-10-15 00:00:00

  • Effects of flanking sequences and cellular context on subcellular behavior and pathology of mutant HTT.

    abstract::Huntington's disease (HD) is caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is necessary to cause pathology and formation of HTT aggregates. Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate formation. By addressing the sufficiency questi...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddaa001

    authors: Chongtham A,Bornemann DJ,Barbaro BA,Lukacsovich T,Agrawal N,Syed A,Worthge S,Purcell J,Burke J,Chin TM,Marsh JL

    更新日期:2020-03-13 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

  • Mutant HSPB8 causes motor neuron-specific neurite degeneration.

    abstract::Missense mutations (K141N and K141E) in the alpha-crystallin domain of the small heat shock protein HSPB8 (HSP22) cause distal hereditary motor neuropathy (distal HMN) or Charcot-Marie-Tooth neuropathy type 2L (CMT2L). The mechanism through which mutant HSPB8 leads to a specific motor neuron disease phenotype is curre...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq234

    authors: Irobi J,Almeida-Souza L,Asselbergh B,De Winter V,Goethals S,Dierick I,Krishnan J,Timmermans JP,Robberecht W,De Jonghe P,Van Den Bosch L,Janssens S,Timmerman V

    更新日期:2010-08-15 00:00:00

  • GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling.

    abstract::Grb10-Interacting GYF Protein 2 (GIGYF2) was initially identified through its interaction with Grb10, an adapter protein that binds activated IGF-I and insulin receptors. The GIGYF2 gene maps to human chromosome 2q37 within a region linked to familial Parkinson's disease (PARK11 locus), and association of GIGYF2 mutat...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddp430

    authors: Giovannone B,Tsiaras WG,de la Monte S,Klysik J,Lautier C,Karashchuk G,Goldwurm S,Smith RJ

    更新日期:2009-12-01 00:00:00

  • SNV identification from single-cell RNA sequencing data.

    abstract::Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz207

    authors: Schnepp PM,Chen M,Keller ET,Zhou X

    更新日期:2019-11-01 00:00:00