Abstract:
:Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alpha 1(V) gene (COL5A1) locus cosegregated with the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three generation family. Affected family members, who had classical features including joint hyperextensibility, fragile skin, and widened, atrophic scars, were heterozygous for a 4 bp deletion at positions from +3 to +6 of intron 65, which resulted in removal of exon 65 sequences from processed mRNAs. Since exon 65 encodes 78 residues of the carboxyl propeptide, the expected result of this mutation is reduced efficiency in incorporating mutant pro alpha 1(V) chains into type V collagen molecules and reduced type V collagen synthesis. These studies indicate that heterozygous mutations in COL5A1 can result in EDS type I. However, linkage studies in other EDS I families indicate the disorder is heterogeneous; linkage to both COL5A1 and COL5A2 was excluded in two other families with EDS I while a fourth family was concordant for linkage to COL5A1 (Z = 2.11; theta = 0.00).
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Wenstrup RJ,Langland GT,Willing MC,D'Souza VN,Cole WGdoi
10.1093/hmg/5.11.1733subject
Has Abstractpub_date
1996-11-01 00:00:00pages
1733-6issue
11eissn
0964-6906issn
1460-2083pii
6w0158journal_volume
5pub_type
杂志文章abstract::Nebulin is a large skeletal muscle protein wound around the thin filaments, with its C-terminus embedded within the Z-disk and its N-terminus extending out toward the thin filament pointed end. While nebulin's C-terminus has been implicated in both sarcomeric structure and function as well as the development of nemali...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz016
更新日期:2019-05-15 00:00:00
abstract::The striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin, a giant molecule that contains several immunoglobulin (Ig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.7.1329
更新日期:1999-07-01 00:00:00
abstract::Osteoarthritis is a common, complex disease with no curative therapy. In this review, we summarize current knowledge on disease aetiopathogenesis and outline genetics and genomics approaches that are helping catalyse a much-needed improved understanding of the biological underpinning of disease development and progres...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddx302
更新日期:2017-10-01 00:00:00
abstract::A 1.5 Mb duplication within 17p11.2 is the major mutation causing both autosomal dominant and sporadic Charcot-Marie-Tooth disease type 1A (CMT1A). An independent origin for the mutation in each family has been postulated. The proposed genetic mechanism causing the CMT1A duplication is unequal nonsister chromatid exch...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.12.2031
更新日期:1993-12-01 00:00:00
abstract::Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a frequent cause of Parkinson's disease (PD). Nonetheless, the physiological role of LRRK2 remains unclear. Here, we demonstrate that LRRK2 participates in canonical Wnt signaling as a scaffold. LRRK2 interacts with key Wnt signaling proteins of th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds342
更新日期:2012-11-15 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::Recent genome-wide association studies (GWAS) have identified a number of novel genetic associations with complex human diseases. In spite of these successes, results from GWAS generally explain only a small proportion of disease heritability, an observation termed the 'missing heritability problem'. Several sources f...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds021
更新日期:2012-05-01 00:00:00
abstract::Protein engineering is a means to optimize protein therapeutics developed for the treatment of so far incurable diseases including cancers and genetic disorders. Here we report on an engineering approach in which we successfully increased the catalytic rate constant of an enzyme that is presently evaluated in enzyme r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz020
更新日期:2019-06-01 00:00:00
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
更新日期:2009-12-01 00:00:00
abstract::Recent prospective analysis identified secretory phospholipase A(2)-IIa (sPLA(2)IIa) as a coronary artery disease (CAD) risk predictor. This study aimed to examine the relationship between serum levels of sPLA(2)IIa and variation in the sPLA(2)IIa gene (PLA2G2A) in a cohort of patients with Type II diabetes (T2D) mell...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi453
更新日期:2006-01-15 00:00:00
abstract::Recent genome-wide association studies (GWAS) have revealed genetic risk factors in autoimmune and inflammatory disorders. Several of the associated genes and underlying pathways are shared by various autoimmune diseases. Rheumatoid arthritis (RA) and coeliac disease (CD) are two autoimmune disorders which have common...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp365
更新日期:2009-11-01 00:00:00
abstract::Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disease caused by mutations in the gene encoding protein kinase C gamma (PKC gamma). We report an SCA14 family with a novel deletion of a termination-codon-containing region, resulting in a missense change and a C-terminal 13-amino-acid extension with inc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp298
更新日期:2009-10-01 00:00:00
abstract::X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder with impaired very long-chain fatty acid (VLCFA) metabolism. The disease-associated ABCD1 (ALD) gene encodes a peroxisomal membrane protein, which belongs to the superfamily of ATP-binding cassette transporters. Several treatment regimes have...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.22.2701
更新日期:2002-10-15 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
pub_type: 杂志文章
doi:10.1093/hmg/ddl099
更新日期:2006-06-01 00:00:00
abstract::Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu556
更新日期:2015-03-01 00:00:00
abstract::Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and the meiosis is resumed by the preovulatory surge of luteinizing hormone. The in vivo functional roles of cyclin-dependent kinases (Cdks) during the resumption of meiosis in mammalian oocytes are largely unknown. Prev...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds061
更新日期:2012-06-01 00:00:00
abstract::Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in underst...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx006
更新日期:2017-03-01 00:00:00
abstract::A candidate gene for X-linked adrenoleukodystrophy (ALD) has been identified via positional cloning strategies. We now report messenger RNA expression in fibroblasts from 6 unrelated ALD patients. Four patients lacked the normal 4.2 kb transcript, three of them having deletions of the ALD gene. A fifth patient with a ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.11.1949
更新日期:1993-11-01 00:00:00
abstract::Melanomas contain high frequencies of tumorigenic cells and their tumorigenic capacity resides in several distinct subpopulations within melanoma. Since their metastatic potential is linked to their ability to recruit lymphatic vessels, we aimed at identifying lymphangiogenic subpopulations by comparative in vitro ana...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds171
更新日期:2012-08-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin along muscle fibers. An attractive therapeutic avenue for DMD consists in the upregulation of utrophin A, a protein with high sequence identity and functional redundancy with dystrophin. Recent work has shown that pharmacological interventions th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu535
更新日期:2015-03-01 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by the expansion of a polyglutamine tract within the SCA1 product, ataxin-1. Previously, using transgenic mice, it was demonstrated that in order for a mutant allele of ataxin-1 to cause disease it must be transported to the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.1.25
更新日期:2001-01-01 00:00:00
abstract::Paraoxonase is an arylesterase enzyme that is expressed in the liver and found in the circulation in association with apoA1 and the high-density lipoprotein, and prevents the accumulation of oxidized lipids in low-density lipoproteins in vitro. Common polymorphisms in genes encoding paraoxonase are established risk fa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi428
更新日期:2006-01-01 00:00:00
abstract::Loss-of-function mutations of the X-chromosome gene UPF3B cause male neurodevelopmental disorders (NDDs) via largely unknown mechanisms. We investigated initially by interrogating a novel synonymous UPF3B variant in a male with absent speech. In silico and functional studies using cell lines derived from this individu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa151
更新日期:2020-08-29 00:00:00
abstract::Familial infantile myasthenia is an autosomal recessive disorder, recently classified as congenital myasthenic syndrome type Ia. Onset of symptoms is at birth to early childhood with significant myasthenic weakness and possible respiratory distress, followed later in life by symptoms of mild to moderate myasthenia. Th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.4.635
更新日期:1997-04-01 00:00:00
abstract::The chromosome region 17p13.3 is thought to encode a tumour suppressor gene involved in sporadic breast cancer and other malignancies. Physical ordering of markers has been carried out by a series of multicolour fluorescent in situ hybridisation (FISH) experiments, using isolated yeast artificial chromosomes (YACs) an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.11.2047
更新日期:1995-11-01 00:00:00
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
更新日期:2010-04-01 00:00:00
abstract::X-linked dyskeratosis congenita (X-DC) is caused by mutations in the housekeeping nucleolar protein dyskerin. Amino acid changes associated with X-DC are remarkably heterogeneous. Peripheral mononuclear blood cells and fibroblasts isolated from X-DC patients harbor lower steady-state telomerase RNA (TER) levels and sh...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr504
更新日期:2012-02-15 00:00:00
abstract::Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma. The majority of these mutations occur de novo and differ from one patient to another. Cytogenetics and Southern blotting were shown to detect less than 15% of constitutional rearrangements. In this study we used the polymerase chain...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.975
更新日期:1993-07-01 00:00:00
abstract::Losing of ovarian functions prior to natural menopause age causes female infertility and early menopause. Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity before 40 years of age. Known genetic causes account for 25-30% of POI cases, demonstrating the high genetic heterogeneity of POI an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa153
更新日期:2020-09-29 00:00:00
abstract::p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. p53 family members execute various functions, such as apoptosis induction and cell cycle arrest, by modulating transcriptional regulation. Therefore, the direct transcriptional targets of the p5...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt673
更新日期:2014-06-01 00:00:00