Abstract:
:A significant minority of degenerative dementias lack distinctive inclusion bodies, plagues or tangles on pathological examination. Half of these cases have a positive family history of dementia. We have studied the largest published family with such a dementia and mapped the disease locus to a 12 cM region of chromosome 3 spanning the centromere. Haplotype analysis demonstrates a common region shared between all affected individuals between the markers D3S1284 and D3S1603. Like a number of other late onset neurodegenerative diseases, the disease presents at an earlier age when paternally inherited.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Brown J,Ashworth A,Gydesen S,Sorensen A,Rossor M,Hardy J,Collinge Jdoi
10.1093/hmg/4.9.1625subject
Has Abstractpub_date
1995-09-01 00:00:00pages
1625-8issue
9eissn
0964-6906issn
1460-2083journal_volume
4pub_type
杂志文章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
更新日期:1996-12-01 00:00:00
abstract::We have identified a rare mutation (T-45C) in the low density lipoprotein (LDL)-receptor gene in a Welsh patient with a clinical diagnosis of heterozygous familial hypercholesterolaemia (FH). The mutation is in the proximal Sp1 binding site in repeat 3 of the 42 bp region of the promoter required for sterol-dependent ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.11.2125
更新日期:1995-11-01 00:00:00
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
更新日期:2010-08-15 00:00:00
abstract::Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome which affects thyroid C cells, and with variable frequency, the adrenal medulla, parathyroid and enteric autonomic ganglia. The syndrome is due to germline mutation in the receptor tyrosine kinase gene, RET. We have recently shown an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.10.1771
更新日期:1994-10-01 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
pub_type: 杂志文章
doi:10.1093/hmg/ddi381
更新日期:2005-11-15 00:00:00
abstract::Research of cilia has gained significant momentum in the last 15 years, as an increasing number of human genetic diseases were found to be caused by disruption of a protein that localizes to cilia. These ciliopathies are as diverse as the functions of the associated proteins, covering a spectrum of overlapping phenoty...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddr354
更新日期:2011-10-15 00:00:00
abstract::Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage disorder of childhood, is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated (palmitoylated) proteins and its mutation causes abnormal intracellular accumulation of fatty-acy...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl105
更新日期:2006-06-01 00:00:00
abstract::The chromosome 22q11 region is susceptible to rearrangements that are associated with congenital anomaly disorders and malignant tumors. Three congenital anomaly disorders, cat-eye syndrome, der() syndrome and velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) are associated with tetrasomy, trisomy or monosomy, ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.7.1157
更新日期:1999-07-01 00:00:00
abstract::The minibrain (mnb) gene of Drosophila melanogaster encodes a serine-threonine protein kinase with an essential role in postembryonic neurogenesis. A corresponding human gene with similar function to mnb could provide important insights into both normal brain development and the abnormal brain development and mental r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.9.1305
更新日期:1996-09-01 00:00:00
abstract::We recently reported that mutations in the widely expressed nuclear protein TOPORS (topoisomerase I-binding arginine/serine rich) are associated with autosomal dominant retinal degeneration. However, the precise localization and a functional role of TOPORS in the retina remain unknown. Here, we demonstrate that TOPORS...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq543
更新日期:2011-03-01 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
pub_type: 杂志文章
doi:10.1093/hmg/ddl099
更新日期:2006-06-01 00:00:00
abstract::Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.3.355
更新日期:1998-03-01 00:00:00
abstract::In human type 1 diabetes (T1D) and in its murine model, the major histocompatibility complex (MHC) class II molecules, human leukocyte antigens (HLA)-DQ and -DR and their murine orthologues, IA and IE, are the major genetic determinants. In this report, we have ranked HLA class II molecule-associated T1D risk in a two...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.19.2025
更新日期:2001-09-15 00:00:00
abstract::Ribonuclease H2 plays an essential role for genome stability as it removes ribonucleotides misincorporated into genomic DNA by replicative polymerases and resolves RNA/DNA hybrids. Biallelic mutations in the genes encoding the three RNase H2 subunits cause Aicardi-Goutières syndrome (AGS), an early-onset inflammatory ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu319
更新日期:2014-11-15 00:00:00
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
更新日期:1995-10-01 00:00:00
abstract::G protein-coupled receptor 154 (GPR154) is a recently discovered asthma susceptibility gene upregulated in the airways of asthma patients. We previously observed increased pulmonary mRNA expression of the murine ortholog Gpr154 in a mouse model of ovalbumin (OVA)-induced inflammation. However, the expression profile o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl090
更新日期:2006-05-15 00:00:00
abstract::Mitochondria contain a dedicated translation system, which is responsible for the intramitochondrial synthesis of 13 mitochondrial DNA (mtDNA)-encoded polypeptides essential for the biogenesis of oxidative phosphorylation (OXPHOS) complexes I and III-V. Mutations in nuclear genes encoding factors involved in mitochond...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy441
更新日期:2019-05-01 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
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddl057
更新日期:2006-04-15 00:00:00
abstract::We introduced a targeted single base deletion at codon 307 of the rds-peripherin gene in mice, similar mutations being known to cause autosomal dominant retinitis pigmentosa (RP) in man. Histopathological and electroretinographic analysis indicate that the retinopathy in mice homozygous for the codon 307 mutation appe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.9.1005
更新日期:2002-05-01 00:00:00
abstract::To enhance our understanding of the autosomal recessive limb-girdle muscular dystrophy (LGMD), patients from six genetically distinct forms (LGMD2A to LGMD2F) were studied with antibodies directed against four sarcoglycan subunits (alpha-, beta-, gamma-, delta-SG), dystrophin, beta-dystroglycan (beta-DG) and merosin. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.12.1963
更新日期:1996-12-01 00:00:00
abstract::The X-linked retinitis pigmentosa protein RP2 is a GTPase activating protein (GAP) for the small GTPase Arl3 and both proteins are implicated in the traffic of proteins to the primary cilia. Here, we show that RP2 can facilitate the traffic of the Gβ subunit of transducin (Gβ1). Glutathione S-transferase (GST)-RP2 pul...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr520
更新日期:2012-02-15 00:00:00
abstract::Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.12.2069
更新日期:1997-11-01 00:00:00
abstract::Coronary heart disease (CHD) is the leading cause of death worldwide. Mitochondrial genetic determinant for the development of CHD remains poorly explored. We report there the clinical, genetic, molecular and biochemical characterization of a four-generation Chinese family with maternally inherited CHD. Thirteen of 32...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt256
更新日期:2013-10-15 00:00:00
abstract::Meta-analysis of genome-wide association studies has resulted in the identification of hundreds of genetic variants associated with growth and stature. Determining how these genetic variants influence growth is important, but most are non-coding, and there is little understanding of how these variants contribute to ad...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddw165
更新日期:2016-08-01 00:00:00
abstract::P/Q-type voltage-gated calcium channels are regulated, in part, through the cytoplasmic C-terminus of their alpha1A subunit. Genetic absence or alteration of the C-terminus leads to abnormal channel function and neurological disease. Here, we show that the terminal 60-75 kDa of the endogenous alpha1A C-terminus is cle...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl080
更新日期:2006-05-15 00:00:00
abstract::FMR1 protein expression was studied in different tissues. In human, monkey and murine tissues, high molecular mass FMR1 proteins (67-80 kDa) are found, as shown in lymphoblastoid cells lines. The identity of these proteins was confirmed by their absence in tissues from patients with the fragile X syndrome and a FMR1 k...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.5.895
更新日期:1995-05-01 00:00:00
abstract::Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of hace1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. Hace1 promotes the stability of Nrf2 and thus plays an im...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx394
更新日期:2018-01-15 00:00:00
abstract::The Vesicle-associated membrane protein (VAMP)-Associated Protein B (VAPB) is the causative gene of amyotrophic lateral sclerosis 8 (ALS8) in humans. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of motor neurons leading to spasticity, muscle atrophy an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt118
更新日期:2013-07-01 00:00:00
abstract::Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg266
更新日期:2003-10-01 00:00:00
abstract::Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv637
更新日期:2016-03-01 00:00:00