Abstract:
:Identification of genes associated with pain insensitivity syndromes can increase the understanding of the pathways involved in pain and contribute to the understanding of how sensory pathways relate to other neurological functions. In this report we describe the mapping and identification of the gene responsible for loss of deep pain perception in a large family from northern Sweden. The loss of pain perception in this family is characterized by impairment in the sensing of deep pain and temperature but with normal mental abilities and with most other neurological responses intact. A severe reduction of unmyelinated nerve fibers and a moderate loss of thin myelinated nerve fibers are observed in the patients. Thus the cases in this study fall into the class of patients with loss of pain perception with underlying peripheral neuropathy. Clinically they best fit into HSAN V. Using a model of recessive inheritance we identified an 8.3 Mb region on chromosome 1p11.2-p13.2 shared by the affected individuals in the family. Analysis of functional candidate genes in the disease critical region revealed a mutation in the coding region of the nerve growth-factor beta (NGFB) gene specific for the disease haplotype. This NGF mutation seems to separate the effects of NGF involved in development of central nervous system functions such as mental abilities, from those involved in peripheral pain pathways. This mutation could therefore potentially provide an important tool to study different roles of NGF, and of pain control.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Einarsdottir E,Carlsson A,Minde J,Toolanen G,Svensson O,Solders G,Holmgren G,Holmberg D,Holmberg Mdoi
10.1093/hmg/ddh096subject
Has Abstractpub_date
2004-04-15 00:00:00pages
799-805issue
8eissn
0964-6906issn
1460-2083pii
ddh096journal_volume
13pub_type
杂志文章abstract::Mutations in the WNK1 gene cause Gordon's syndrome, a rare Mendelian form of hypertension. We assessed whether common WNK1 variants might also contribute to essential hypertension (EH), a multifactorial disorder affecting > 25% of the adult population worldwide. A panel of 19 single nucleotide polymorphisms (SNPs) spa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi187
更新日期:2005-07-01 00:00:00
abstract::Understanding the role of the epigenome in protein-misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable response of the disease population to therapeutics. An ever-growing body of evidence has shown ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz026
更新日期:2019-06-15 00:00:00
abstract::α-Mannosidosis is a lysosomal storage disorder caused by mutations in the MAN2B1 gene. The clinical presentation of α-mannosidosis is variable, but typically includes mental retardation, skeletal abnormalities and immune deficiency. In order to understand the molecular aetiology of α-mannosidosis, we describe here the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr167
更新日期:2011-07-01 00:00:00
abstract::Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz110
更新日期:2019-09-15 00:00:00
abstract::Prader-Willi syndrome (PWS) is caused by the loss of expression of imprinted genes in chromosome 15q11-q13. Affected individuals exhibit neonatal hypotonia, developmental delay and childhood-onset obesity. Necdin, a protein implicated in the terminal differentiation of neurons, is the only PWS candidate gene to reduce...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.12.1813
更新日期:2000-07-22 00:00:00
abstract::Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv183
更新日期:2015-08-15 00:00:00
abstract::DiGeorge syndrome, and more widely the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. A critical region of 500 kb has been delimited within which maps the breakpoint of a balanced translocation associated with mild CATCH 22 phenotypes. We report the isolation from this critical re...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.5.633
更新日期:1996-05-01 00:00:00
abstract::Paraspeckles are nuclear bodies formed by a set of specialized proteins assembled on the long non-coding RNA NEAT1; they have a role in nuclear retention of hyperedited transcripts and are associated with response to cellular stress. Fused in sarcoma (FUS) protein, linked to a number of neurodegenerative disorders, is...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt622
更新日期:2014-05-01 00:00:00
abstract::Uterine leiomyomata (UL), also known as fibroids, are the most common pelvic tumors in women of reproductive age and are the primary indication for hysterectomy in the USA. Many lines of evidence indicate a strong genetic component to the development of these tumors. In fact, approximately 40% of UL have non-random, t...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm043
更新日期:2007-04-15 00:00:00
abstract::Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregati...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx260
更新日期:2017-10-01 00:00:00
abstract::Proteins with iron-sulfur (Fe-S) clusters participate in multiple metabolic pathways throughout the cell. The mitochondrial ABC half-transporter Abcb7, which is mutated in X-linked sideroblastic anemia with ataxia in humans, is a functional ortholog of yeast Atm1p and is predicted to export a mitochondrially derived m...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl012
更新日期:2006-03-15 00:00:00
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
更新日期:2014-10-01 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::Imputation is commonly used in genome-wide association studies to expand the set of genetic variants available for analysis. Larger and more diverse reference panels, such as the final Phase 3 of the 1000 Genomes Project, hold promise for improving imputation accuracy in genetically diverse populations such as Hispani...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw174
更新日期:2016-08-01 00:00:00
abstract::The apolipoprotein A5 gene (APOA5 ) has been shown to play an important role in determining plasma triglyceride concentrations in humans. We describe here a novel variant, c.553G>T, in the apolipoprotein A5 gene that is associated with hypertriglyceridemia. In contrast to some other polymorphisms, which occur in non-c...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg255
更新日期:2003-10-01 00:00:00
abstract::Dominant mutations in the gene encoding the ubiquitously-expressed splicing factor PRPF31 cause retinitis pigmentosa, a form of hereditary retinal degeneration, with reduced penetrance. We and others have previously shown that penetrance is tightly correlated with PRPF31 expression, as lymphoblastoid cell lines (LCLs)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn212
更新日期:2008-10-15 00:00:00
abstract::The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to doub...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds173
更新日期:2012-08-01 00:00:00
abstract::A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha-synuclein gene were amplified by PCR from i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.4.751
更新日期:1998-04-01 00:00:00
abstract::We have studied 21 families with Wilson disease (WND), using restriction fragment length polymorphisms (RFLPs) in the 13q14.3 region, to measure linkage of these markers to the disease locus. In addition to previously described markers, we include linkage data for a newly isolated marker (D13S86) and an established ma...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.9.1401
更新日期:1993-09-01 00:00:00
abstract::Mammalian sex chromosomes are thought to be descended from a homologous pair of autosomes: a testis-determining allele which defined the Y chromosome arose, recombination between the nascent X and Y chromosomes became restricted and the Y chromosome gradually lost its non-essential genetic functions. This model was or...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.3.429
更新日期:1998-03-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD is characterized by mutations in the dystrophin gene that result in a loss of the dystrophin protein. Loss of dystrophin causes an associated reduction in proteins of the dystrophin glycoprotein...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz044
更新日期:2019-07-01 00:00:00
abstract::Gene amplification plays a critical role in tumor progression. Hence, understanding the factors triggering this process in human cancers is an important concern. Unfortunately, the structures formed at early stages are usually unavailable for study, hampering the identification of the initiating events in tumors. Here...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.23.2887
更新日期:2002-11-01 00:00:00
abstract::Myotonic dystrophy (DM) is the most common form of inherited neuromuscular disease in adults and is characterized by progressive muscle wasting and myotonia. The mutation responsible for DM has been identified as the amplification of a polymorphic (CTG)n repeat in the 3' untranslated region of a gene encoding a serine...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.6.1063
更新日期:1995-06-01 00:00:00
abstract::As the powerhouses of the eukaryotic cell, mitochondria must maintain their genomes which encode proteins essential for energy production. Mitochondria are characterized by guanine-rich DNA sequences that spontaneously form unusual three-dimensional structures known as G-quadruplexes (G4). G4 structures can be problem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa043
更新日期:2020-05-28 00:00:00
abstract::Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adol...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv465
更新日期:2016-01-15 00:00:00
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
更新日期:2000-08-12 00:00:00
abstract::Mutations in subunits or regulators of cohesin cause a spectrum of disorders in humans known as the 'cohesinopathies'. Cohesinopathies, including the best known example Cornelia de Lange syndrome (CdLS), are characterized by broad spectrum, multifactorial developmental anomalies. Heart defects occur at high frequency ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv402
更新日期:2015-12-15 00:00:00
abstract::Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies sugg...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw219
更新日期:2016-09-01 00:00:00
abstract::Xq28 has been of special interest in human genetics because a large number of diseases map to this region. As a step in the molecular analysis of the as yet uncloned disease genes, and as a test for the detailed analysis of larger regions of the genome, we have constructed YAC clone contigs covering the 7.5 Mb region ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.12.2137
更新日期:1994-12-01 00:00:00
abstract::We have used inbred and congenic rat strains in F(2) segregation studies to discover epistasis in a polygenic model of hypertension. Previously, we have found evidence that the presence of a blood pressure quantitative trait locus (QTL) on chromosome 1 is conditional upon the allele status of chromosome 10. To prove t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg041
更新日期:2003-02-15 00:00:00