Abstract:
:Lysosomes, melanosomes and platelet-dense granules are abnormal in the mouse hypopigmentation mutant pearl. The beta3A subunit of the AP-3 adaptor complex, which likely regulates protein trafficking in the trans - Golgi network/endosomal compartments, was identified as a candidate for the pearl gene by a positional/candidate cloning approach. Mutations, including a large internal tandem duplication and a deletion, were identified in two respective pearl alleles and are predicted to abrogate function of the beta3A protein. Significantly lowered expression of altered beta3A transcripts occurred in kidney of both mutant alleles. The several distinct pearl phenotypes suggest novel functions for the AP-3 complex in mammals. These experiments also suggest mutations in AP-3 subunits as a basis for unique forms of human Hermansky-Pudlak syndrome and congenital night blindness, for which the pearl mouse is an appropriate animal model.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Feng L,Seymour AB,Jiang S,To A,Peden AA,Novak EK,Zhen L,Rusiniak ME,Eicher EM,Robinson MS,Gorin MB,Swank RTdoi
10.1093/hmg/8.2.323subject
Has Abstractpub_date
1999-02-01 00:00:00pages
323-30issue
2eissn
0964-6906issn
1460-2083pii
ddc031journal_volume
8pub_type
杂志文章abstract::Neural tube defects (NTDs) are birth defects that can be disabling or lethal and are second in their prevalence after cardiac defects among major human congenital malformations. Spina bifida is a NTD where the spinal cord is dysplastic, and the overlying spinal column is absent. At present, the molecular mechanisms un...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm333
更新日期:2008-02-15 00:00:00
abstract::Cilia are evolutionarily conserved organelles endowed with essential physiological and developmental functions. In humans, disruption of cilia motility or signaling leads to complex pleiotropic genetic disorders called ciliopathies. Cilia motility requires the assembly of multi-subunit motile components such as dynein...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt445
更新日期:2014-02-01 00:00:00
abstract::Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), characterized by microcephaly, chromosomal instability, radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin; however, 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi482
更新日期:2006-03-01 00:00:00
abstract::We studied a consanguineous Palestinian Arab family segregating an autosomal recessive progressive myoclonus epilepsy (PME) with early ataxia. PME is a rare, often fatal syndrome, initially responsive to antiepileptic drugs which over time becomes refractory and can be associated with cognitive decline. Linkage analys...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv171
更新日期:2015-08-15 00:00:00
abstract::Leukodystrophies are rare diseases caused by defects in the genes coding for lysosomal enzymes that degrade several glycosphingolipids. Gene therapy for leukodystrophies requires efficient distribution of the missing enzymes in CNS tissues to prevent demyelination and neurodegeneration. In this work, we targeted the e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq099
更新日期:2010-06-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a high spontaneous mutation rate and no effective treatment, hence development of genetic based therapies is an important goal. We report that expression of a recombinant human minidystrophin cDNA, compatible with current viral vectors, can...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.8.1245
更新日期:1995-08-01 00:00:00
abstract::Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl451
更新日期:2007-01-15 00:00:00
abstract::Mutations in gigaxonin were identified in giant axonal neuropathy (GAN), an autosomal recessive disorder. To understand how disruption of gigaxonin's function leads to neurodegeneration, we ablated the gene expression in mice using traditional gene targeting approach. Progressive neurological phenotypes and pathologic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl069
更新日期:2006-05-01 00:00:00
abstract::Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy caused by a polyalanine expansion mutation in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)(6) encodes the first 6 alanines in a homopolymeric stretch of 10 alanines. In most patie...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq559
更新日期:2011-03-15 00:00:00
abstract::Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two het...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw041
更新日期:2016-04-15 00:00:00
abstract::Mutations in the human ortholog of Drosophila patched (PTCH) have been identified in patients with autosomal dominant nevoid basal cell carcinoma syndrome (NBCCS), characterized by minor developmental anomalies and an increased incidence of cancers such as medulloblastoma and basal cell carcinoma. We identified many i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi369
更新日期:2005-11-15 00:00:00
abstract::Huntington's disease shares a common molecular basis with eight other neurodegenerative diseases, expansion of an existing polyglutamine tract. In each case, this repeat tract occurs within otherwise unrelated proteins. These proteins show widespread and overlapping patterns of expression in the brain and yet the dise...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp455
更新日期:2009-12-15 00:00:00
abstract::Gamma glutamyl cysteine ligase (GCL) is the rate-limiting enzyme for intracellular glutathione (GSH) synthesis. The GSH concentration and GCL activity are declining with age in the central nervous system (CNS), and is accompanied by elevated reactive oxygen species (ROS). To study the biological effects of low GSH lev...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx040
更新日期:2017-04-01 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
pub_type: 杂志文章
doi:10.1093/hmg/ddy008
更新日期:2018-03-01 00:00:00
abstract::Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp311
更新日期:2009-10-01 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
pub_type: 杂志文章
doi:10.1093/hmg/ddaa246
更新日期:2021-01-21 00:00:00
abstract::Linkage analysis of type 1 diabetes sib pair families (n = 334) has suggested two separate regions of human chromosome 6q are linked to disease (designated IDDM5 and IDDM8). To test if these are false positive results, all available sib pair families (n = 429) were typed using a 92% informative map of chromosome 6q an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.7.1071
更新日期:1996-07-01 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine tract expansion. In SCA1, the expanded polyglutamine tract is in the ataxin-1 (ATXN1) protein. ATXN1 is part of an in vivo complex with retinoid acid receptor-related orphan receptor alpha (Rora)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr108
更新日期:2011-06-01 00:00:00
abstract::Mutations in ATP13A2 (PARK9) cause Kufor-Rakeb syndrome (KRS) characterized by juvenile-onset parkinsonism, pyramidal signs and dementia. PARK9 belongs to type 5 P-type ATPase with its putative function as a cation transporter. Loss of PARK9 leads to lysosomal dysfunction and subsequent α-synuclein (α-Syn) accumulatio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt572
更新日期:2014-06-01 00:00:00
abstract::Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using ...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddr325
更新日期:2011-10-15 00:00:00
abstract::Eiken syndrome is a rare autosomal recessive skeletal dysplasia. We identified a truncation mutation in the C-terminal cytoplasmic tail of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) type 1 receptor (PTHR1) gene as the cause of this syndrome. Eiken syndrome differs from Jansen and Blomstrand chondrodyspl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi001
更新日期:2005-01-01 00:00:00
abstract::Glutamine (Q) expansion diseases are a family of degenerative disorders caused by the lengthening of CAG triplet repeats present in the coding sequences of seemingly unrelated genes whose mutant proteins drive pathogenesis. Despite all the molecular evidence for the genetic basis of these diseases, how mutant poly-Q p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds246
更新日期:2012-10-01 00:00:00
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
更新日期:2010-04-15 00:00:00
abstract::Rett syndrome (RTT) is a neurodevelopmental disorder with no efficient treatment that is caused in the majority of cases by mutations in the gene methyl-CpG binding-protein 2 (MECP2). RTT becomes manifest after a period of apparently normal development and causes growth deceleration, severe psychomotor impairment and ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq563
更新日期:2011-03-15 00:00:00
abstract::A randomization procedure to evaluate the significance level and the false-discovery rate in complex microarray experiments is proposed. A related graph can be used to compare different test statistics that can be used to analyze the same experiment. This graph is closely related to receiver operator characteristic (R...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.19.2223
更新日期:2002-09-15 00:00:00
abstract::Trinucleotide repeats at five disease loci (DM, DRPLA, HD, SBMA and SCA1) were surveyed in phenotypically normal individuals from three continental populations. This is the first analysis to examine the population dynamics of these five disease-related trinucleotide repeats in the same individuals from worldwide popul...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.9.1485
更新日期:1995-09-01 00:00:00
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
更新日期:2019-11-01 00:00:00
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
更新日期:2018-03-01 00:00:00
abstract::Adolescent idiopathic scoliosis (AIS) is a complex inherited spinal deformity whose etiology has been elusive. While common genetic variants are associated with AIS, they explain only a small portion of disease risk. To explore the role of rare variants in AIS susceptibility, exome sequence data of 391 severe AIS case...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv463
更新日期:2016-01-01 00:00:00
abstract::Parkin E3 ubiquitin-ligase activity and its role in mitochondria homeostasis are thought to play a role in Parkinson's disease (PD). We now report that AF-6 is a novel parkin interacting protein that modulates parkin ubiquitin-ligase activity and mitochondrial roles. Parkin interacts with the AF-6 PDZ region through i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt058
更新日期:2013-05-15 00:00:00