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

abstract：:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of ...

journal_title：Human molecular genetics

authors： Tao Z,Wang H,Xia Q,Li K,Li K,Jiang X,Xu G,Wang G,Ying Z

更新日期：2015-05-01 00:00:00

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

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

abstract：:Mutations in transforming growth factor beta (TGFβ) receptor type II (TGFBR2) cause Loeys-Dietz syndrome, characterized by craniofacial and cardiovascular abnormalities. Mice with a deletion of Tgfbr2 in cranial neural crest cells (Tgfbr2(fl/fl);Wnt1-Cre mice) develop cleft palate as the result of abnormal TGFβ signal...

journal_title：Human molecular genetics

authors： Iwata J,Suzuki A,Pelikan RC,Ho TV,Sanchez-Lara PA,Chai Y

更新日期：2014-01-01 00:00:00

abstract：:Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. It remains u...

journal_title：Human molecular genetics

authors： Saha A,Sarkar C,Singh SP,Zhang Z,Munasinghe J,Peng S,Chandra G,Kong E,Mukherjee AB

更新日期：2012-05-15 00:00:00

abstract：:Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene. This encodes the enzyme ATP:cob(I)alamin adenosyltransferase (ATR), which converts reduced cob(I)alamin to an active adenosylcobalamin cofactor. We recently reported the presence of destabilizing pathogenic mutations that retain some resid...

journal_title：Human molecular genetics

authors： Jorge-Finnigan A,Brasil S,Underhaug J,Ruíz-Sala P,Merinero B,Banerjee R,Desviat LR,Ugarte M,Martinez A,Pérez B

更新日期：2013-09-15 00:00:00

abstract：:Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is reta...

journal_title：Human molecular genetics

authors： Rose FF Jr,Mattis VB,Rindt H,Lorson CL

更新日期：2009-03-15 00:00:00

abstract：:Rett syndrome (RTT) is an X-linked dominant disabling neurodevelopmental disorder caused by loss of function mutations in the MECP2 gene, located at Xq28, which encodes a multifunctional protein. MECP2 expression is regulated in a developmental stage and cell-type-specific manner. The need for tightly controlled MeCP2...

journal_title：Human molecular genetics

authors： Liu J,Francke U

更新日期：2006-06-01 00:00:00

abstract：:BCS1L encodes a homolog of the Saccharomyces cerevisiae bcs1 protein, which has a known role in the assembly of Complex III of the mitochondrial respiratory chain. Phenotypes reported in association with pathogenic BCS1L variants include growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis an...

journal_title：Human molecular genetics

authors： Oláhová M,Ceccatelli Berti C,Collier JJ,Alston CL,Jameson E,Jones SA,Edwards N,He L,Chinnery PF,Horvath R,Goffrini P,Taylor RW,Sayer JA

更新日期：2019-11-15 00:00:00

abstract：:KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone....

journal_title：Human molecular genetics

authors： Pereira F,Barbáchano A,Silva J,Bonilla F,Campbell MJ,Muñoz A,Larriba MJ

更新日期：2011-12-01 00:00:00

abstract：:An intronic GGGGCC (G4C2) hexanucleotide repeat expansion inC9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 RNA can result in five different dipeptide repeat proteins (DPR: poly GA, poly GP, poly GR, ...

journal_title：Human molecular genetics

authors： Lee YB,Baskaran P,Gomez-Deza J,Chen HJ,Nishimura AL,Smith BN,Troakes C,Adachi Y,Stepto A,Petrucelli L,Gallo JM,Hirth F,Rogelj B,Guthrie S,Shaw CE

更新日期：2017-12-15 00:00:00

abstract：:Bloom's syndrome (BS) is an autosomal recessive disorder that is invariably characterized by severe growth retardation and cancer predisposition. The Bloom's syndrome helicase (BLM), mutations of which lead to BS, localizes to promyelocytic leukemia protein bodies and to the nucleolus of the cell, the site of RNA poly...

journal_title：Human molecular genetics

authors： Grierson PM,Lillard K,Behbehani GK,Combs KA,Bhattacharyya S,Acharya S,Groden J

更新日期：2012-03-01 00:00:00

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

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

更新日期：2013-11-01 00:00:00

abstract：:Long range restriction site maps of 13 Mb of mouse chromosome 1 and 11 Mb of human chromosome 1 were constructed using a framework provided by a detailed mouse genetic map. Where an unambiguous gene order could be determined in both species (14 genes), the human and mouse orders were identical. In addition, the distan...

journal_title：Human molecular genetics

authors： Oakey RJ,Watson ML,Seldin MF

更新日期：1992-11-01 00:00:00

abstract：:The genomic instability of persons with Bloom's syndrome (BS) features particularly an increased number of sister-chromatid exchanges (SCEs). The primary cause of the genomic instability is mutation at BLM, which encodes a DNA helicase of the RecQ family. BLM interacts with Topoisomerase IIIalpha (Topo IIIalpha), and ...

journal_title：Human molecular genetics

authors： Hu P,Beresten SF,van Brabant AJ,Ye TZ,Pandolfi PP,Johnson FB,Guarente L,Ellis NA

更新日期：2001-06-01 00:00:00

abstract：:The near completeness of human chromosome sequences is facilitating accurate characterization and assessment of all classes of genomic variation. Particularly, using the DNA reference sequence as a guide, genome scanning technologies, such as microarray-based comparative genomic hybridization (array CGH) and genome-wi...

journal_title：Human molecular genetics

authors： Feuk L,Marshall CR,Wintle RF,Scherer SW

更新日期：2006-04-15 00:00:00

abstract：:Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly u...

journal_title：Human molecular genetics

authors： Godfrey C,Muses S,McClorey G,Wells KE,Coursindel T,Terry RL,Betts C,Hammond S,O'Donovan L,Hildyard J,El Andaloussi S,Gait MJ,Wood MJ,Wells DJ

更新日期：2015-08-01 00:00:00

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

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

abstract：:The congenital malformation split hand/foot (SHFM) is characterized by missing central fingers and dysmorphology or fusion of the remaining ones. Type-1 SHFM is linked to deletions/rearrangements of the DLX5-DLX6 locus and point mutations in the DLX5 gene. The ectrodactyly phenotype is reproduced in mice by the double...

journal_title：Human molecular genetics

authors： Conte D,Garaffo G,Lo Iacono N,Mantero S,Piccolo S,Cordenonsi M,Perez-Morga D,Orecchia V,Poli V,Merlo GR

更新日期：2016-02-15 00:00:00

abstract：:Mutations in the paired-domain transcription factor PAX9 are associated with non-syndromic tooth agenesis that preferentially affects posterior dentition. Of the 18 mutations identified to date, eight are phenotypically well-characterized missense mutations within the DNA-binding paired domain. We determined the struc...

journal_title：Human molecular genetics

authors： Wang Y,Groppe JC,Wu J,Ogawa T,Mues G,D'Souza RN,Kapadia H

更新日期：2009-08-01 00:00:00

abstract：:Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to s...

journal_title：Human molecular genetics

authors： Sankila EM,Pakarinen L,Kääriäinen H,Aittomäki K,Karjalainen S,Sistonen P,de la Chapelle A

更新日期：1995-01-01 00:00:00

abstract：:Spastic paraplegia 35 (SPG35) (OMIM: 612319) or fatty acid hydroxylase-associated neurodegeneration (FAHN) is caused by deficiency of fatty acid 2-hydroxylase (FA2H). This enzyme synthesizes sphingolipids containing 2-hydroxylated fatty acids, which are particularly abundant in myelin. Fa2h-deficient (Fa2h-/-) mice de...

journal_title：Human molecular genetics

authors： Hardt R,Jordans S,Winter D,Gieselmann V,Wang-Eckhardt L,Eckhardt M

更新日期：2021-01-21 00:00:00

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

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

abstract：:Fragile X Syndrome (FXS) is a learning disability seen in individuals who have >200 CGG•CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress...

journal_title：Human molecular genetics

authors： Yudkin D,Hayward BE,Aladjem MI,Kumari D,Usdin K

更新日期：2014-06-01 00:00:00

abstract：:We performed a genome-wide scan for susceptibility loci in bipolar disorder in a study sample colleted from the isolated Finnish population, consisting of 41 families with at least two affected siblings. We identified one distinct locus on 16p12 providing significant evidence for linkage in two-point analysis (Z(max)=...

journal_title：Human molecular genetics

authors： Ekholm JM,Kieseppä T,Hiekkalinna T,Partonen T,Paunio T,Perola M,Ekelund J,Lönnqvist J,Pekkarinen-Ijäs P,Peltonen L

更新日期：2003-08-01 00:00:00

abstract：:Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia/myopathy, respectively. The mechanism by which they disrupt mitochondrial cristae, however...

journal_title：Human molecular genetics

authors： Liu YT,Huang X,Nguyen D,Shammas MK,Wu BP,Dombi E,Springer DA,Poulton J,Sekine S,Narendra DP

更新日期：2020-06-03 00:00:00

abstract：:We have studied the functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. Surprisingly, these cells had an efficient oxidative phosphorylation (OXPHOS); however, when mitochondria from these cells were transferred to an osteosarcoma nuclear backgr...

journal_title：Human molecular genetics

authors： Srivastava S,Barrett JN,Moraes CT

更新日期：2007-04-15 00:00:00

abstract：:Muscular dystrophies are a group of genetic diseases that lead to muscle wasting and, in most cases, premature death. Cytokines and inflammatory factors are released during the disease process where they promote deleterious signaling events that directly participate in myofiber death. Here, we show that p38α, a kinase...

journal_title：Human molecular genetics

authors： Wissing ER,Boyer JG,Kwong JQ,Sargent MA,Karch J,McNally EM,Otsu K,Molkentin JD

更新日期：2014-10-15 00:00:00

abstract：:Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving ...

journal_title：Human molecular genetics

authors： Litchfield K,Sultana R,Renwick A,Dudakia D,Seal S,Ramsay E,Powell S,Elliott A,Warren-Perry M,Eeles R,Peto J,Kote-Jarai Z,Muir K,Nsengimana J,UKTCC.,Stratton MR,Easton DF,Bishop DT,Huddart RA,Rahman N,Turnbull C,

更新日期：2015-02-15 00:00:00

abstract：:Megf7/Lrp4 is a member of the functionally diverse low-density lipoprotein receptor gene family, a class of ancient and highly conserved cell surface receptors with broad functions in cargo transport and cellular signaling. To gain insight into the as yet unknown biological role of Megf7/Lrp4, we have disrupted the ge...

journal_title：Human molecular genetics

authors： Johnson EB,Hammer RE,Herz J

更新日期：2005-11-15 00:00:00

abstract：:Valosin-containing protein (VCP)-associated disease caused by mutations in the VCP gene includes combinations of a phenotypically heterogeneous group of disorders such as hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis. Currently, there are no effe...

journal_title：Human molecular genetics

authors： Llewellyn KJ,Nalbandian A,Jung KM,Nguyen C,Avanesian A,Mozaffar T,Piomelli D,Kimonis VE

更新日期：2014-03-01 00:00:00