Abstract:
:Development of gene therapy for the muscular dystrophies represents a daunting challenge requiring significant advances in our knowledge of the defective genes, muscle promoters, viral vectors, immune system surveillance and methods for systemic delivery of vectors. However, tremendous progress has been made in developing improved viral vectors and avoiding immune reactions against gene transfer. This review summarizes recent progress and highlights problems that must be solved before an effective treatment is available.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Chamberlain JSdoi
10.1093/hmg/11.20.2355subject
Has Abstractpub_date
2002-10-01 00:00:00pages
2355-62issue
20eissn
0964-6906issn
1460-2083journal_volume
11pub_type
杂志文章,评审abstract::Oculodentodigital syndrome (ODD) is a congenital, autosomal dominant disorder which affects the development of the face, eyes, limbs and dentition. Spastic paraparesis is thought to be an occasional manifestation of the disorder. Type III syndactyly, which occurs as part of ODD, has also been reported to occur as an i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.1.123
更新日期:1997-01-01 00:00:00
abstract::In mammals, sperm-oocyte fusion initiates Ca(2+) oscillations leading to a series of events called oocyte activation, which is the first stage of embryo development. Ca(2+) signaling is elicited by the delivery of an oocyte-activating factor by the sperm. A sperm-specific phospholipase C (PLCZ1) has emerged as the lik...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv617
更新日期:2016-03-01 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::Cell pathology in lysosomal storage diseases is characterized by the formation of distended vacuoles with characteristics of lysosomes. Our previous studies in mucopolysaccharidosis type IIIB (MPSIIIB), a disease in which a genetic defect induces the accumulation of undigested heparan sulfate (HS) fragments, led to th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr584
更新日期:2012-04-01 00:00:00
abstract::A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddz196
更新日期:2019-11-21 00:00:00
abstract::Deficiencies in the complex I (CI; NADH-ubiquinone oxidoreductase) of the respiratory chain are frequent causes of mitochondrial diseases and have been associated with other neurodegenerative disorders, such as Parkinson's disease. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex subunit 5 (NDUFA5) is a nuclear-e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt526
更新日期:2014-03-15 00:00:00
abstract::Despite the clinical importance of human aneuploidy, we know little of the causes of mammalian non-disjunction. In part, this reflects the fact that, unlike lower organisms, segregation 'impaired' chromosomes are virtually non-existent in mammals. To address this issue, we have studied the mouse Y chromosome on the BA...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.9.963
更新日期:2001-04-15 00:00:00
abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz094
更新日期:2019-08-15 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::Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2-/-). Although...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq453
更新日期:2011-01-01 00:00:00
abstract::Atopic (allergic) asthma is the most common disease of childhood and is strongly genetic in origin. Many genome-wide screens for asthma and its associated traits have now been carried out, and genetic linkage has been consistently identified in several regions. It is probable that these loci contain major genes influe...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/9.16.2359
更新日期:2000-10-01 00:00:00
abstract::The genes of the piwi family are defined by conserved PAZ and Piwi domains and play important roles in stem-cell self-renewal, RNA silencing and translational regulation in various organisms. Both, mouse and human Piwil2 genes, members of the piwi gene family, are specifically expressed in testis. We report here enhan...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi430
更新日期:2006-01-15 00:00:00
abstract::In the field of muscular dystrophy, advances in understanding the molecular basis of the various disorders in this group have been rapidly translated into readily applicable diagnostic tests, allowing the provision of more accurate prognostic and genetic counselling. The limb-girdle muscular dystrophies (LGMD) have re...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/8.10.1875
更新日期:1999-01-01 00:00:00
abstract::Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We c...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp052
更新日期:2009-04-15 00:00:00
abstract::We report the case of a consanguineous couple who lost four pregnancies associated with skeletal dysplasia. Radiological examination of one fetus was inconclusive. Parental exome sequencing showed that both parents were heterozygous for a novel missense variant, p.(Pro133Leu), in the SLC35D1 gene encoding a nucleotide...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz200
更新日期:2019-11-01 00:00:00
abstract::The RASopathies are a group of genetic syndromes caused by upregulated RAS signaling. Noonan syndrome (NS), the most common entity among the RASopathies, is characterized mainly by short stature, cardiac anomalies and distinctive facial features. Mutations in multiple RAS-MAPK pathway-related genes have been associate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz108
更新日期:2020-07-21 00:00:00
abstract::The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysp...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx421
更新日期:2018-02-01 00:00:00
abstract::The transcription factor SOX10 is mutated in the human neurocristopathy Waardenburg-Shah syndrome (WS4), which is characterized by enteric aganglionosis and pigmentation defects. SOX10 directly regulates genes expressed in neural crest lineages, including the enteric ganglia and melanocytes. Although some SOX10 target...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi442
更新日期:2006-01-15 00:00:00
abstract::The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineag...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr069
更新日期:2011-05-15 00:00:00
abstract::Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the expansion of a CAG repeat in a gene coding for a protein of unknown function. We have raised a polyclonal antibody against a 12 amino acid peptide (residues 2110-2121 of human huntingtin) which specifically recognises huntingtin on West...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.4.481
更新日期:1996-04-01 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
pub_type: 杂志文章
doi:10.1093/hmg/ddu270
更新日期:2014-10-15 00:00:00
abstract::The clearest example of genomic imprinting in humans comes from studies of the Angelman (AS) and Prader-Willi (PWS) syndromes. Although these are clinically distinct disorders, both typically result from a loss of the same chromosomal region, 15q11-q13. AS usually results from either a maternal deletion of this region...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.9.1377
更新日期:1993-09-01 00:00:00
abstract::Osteoarthritis (OA) is a common, painful and debilitating disease of articulating joints resulting from the age-associated loss of cartilage. Well-powered genetic studies have identified a number of DNA polymorphisms that are associated with OA susceptibility. Like most complex trait loci, these OA loci are thought to...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv433
更新日期:2015-12-20 00:00:00
abstract::Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.9.1283
更新日期:2000-05-22 00:00:00
abstract::Down syndrome (DS) is the most common genetic cause of mental retardation and affects many aspects of brain development. DS individuals exhibit an overall reduction in brain size with a disproportionately greater reduction in cerebellar volume. The Ts65Dn mouse is segmentally trisomic for the distal 12-15 Mb of mouse ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.2.195
更新日期:2000-01-22 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::We describe a detection principle for indirect fluorescence in situ hybridization (FISH) methods that with only one or two antibody layers dramatically improves FISH signal intensities. The method uses as a first layer an anti-hapten immunoglobulin [or (strept)avidin] conjugated to peroxidase. The quintessence of the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.529
更新日期:1995-04-01 00:00:00
abstract::Gene transfer studies for the treatment of hemophilia began more than two decades ago. A large body of pre-clinical work evaluated a variety of vectors and target tissues, but by the start of the new millennium it became evident that adeno-associated viral (AAV)-mediated gene transfer to the liver held great promise a...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddv475
更新日期:2016-04-15 00:00:00
abstract::We investigated the population differences in patterns of single nucleotide polymorphisms (SNPs) for a 400 kb olfactory receptor (OR) gene cluster on human chromosome 17p13.3. Samples were drawn from 35 individuals, of four different ethnogeographical origins: Pygmies, Bedouins, Yemenite Jews and Ashkenazi Jews. Of th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.12.1381
更新日期:2002-06-01 00:00:00
abstract::Mutations in GDAP1 lead to recessively or dominantly inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT), indicating that GDAP1 is essential for the viability of cells in the peripheral nervous system. GDAP1 contains domains characteristic of glutathione-S-transferases (GSTs), is located in the outer ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr450
更新日期:2012-01-01 00:00:00