Abstract:
:Primary open-angle glaucoma (POAG) is a complex disorder characterized by a progressive and treatable degeneration of the optic nerve. TIGR/myocilin (MYOC) gene mutations are found in approximately 4% of all POAG patients. Populations with frequent founder effects, such as the French-Canadians, offer unique advantages to implement genetic testing for the disorder. To assess molecular diagnosis for POAG in this population, we determined the prevalence of TIGR/MYOC mutations in 384 unrelated glaucoma patients, 38 ocular hypertensive subjects and 18 affected families (180 patients). We further analyzed the clinical features associated with these variations. Nine coding sequence variants were defined as mutations causing mostly, but not exclusively, POAG. Four families segregated distinct mutations (Gly367Arg, Gln368Stop, Lys423Glu and Pro481Leu), while 14 unrelated glaucoma patients harbored six known mutations (Thr293Lys, Glu352Lys, Gly367Arg, Gln368Stop, Lys423Glu and Ala445Val) and two novel (Ala427Thr and Arg126Trp). The frequencies of these mutations were respectively 3.8% and 22.2% in the unrelated and family studies. The Gly367Arg and Lys423Glu variants caused the earliest ages at onset. When achievable, assessment of relatives of unrelated mutation carriers showed the Arg126Trp and Gly367Arg to be familial. Characteristic allele signatures, indicative of specific founder effects, were observed for five of the six mutations conveyed by at least two patients. Recombination probability estimates suggested that the French-Canadian population had most probably inherited these six mutations from 7-10 Québec settlers. Our data demonstrated that genetic screening for TIGR/MYOC mutations should be offered to glaucoma families and to close relatives of unrelated patients aware of a family history for the disorder.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Faucher M,Anctil JL,Rodrigue MA,Duchesne A,Bergeron D,Blondeau P,Côté G,Dubois S,Bergeron J,Arseneault R,Morissette J,Raymond V,Québec Glaucoma Network.doi
10.1093/hmg/11.18.2077subject
Has Abstractpub_date
2002-09-01 00:00:00pages
2077-90issue
18eissn
0964-6906issn
1460-2083journal_volume
11pub_type
杂志文章abstract::Fragile X Syndrome is the most common form of hereditary mental retardation. It is caused by a large expansion of the CGG trinucleotide repeat (>200 repeats) in the 5'-untranslated region (UTR) of the FMR1 gene that leads to silencing of its transcript. Individuals with CGG repeat expansions approximately between 60 a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm186
更新日期:2007-10-01 00:00:00
abstract::Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1021
更新日期:1997-07-01 00:00:00
abstract::By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA library of a human skeletal muscle, we identified 1945 individual transcripts, 725 of which showed no correspondence with known human genes. We report here the chromosomal localization of 267 of these, obtained by radiation hybrid (RH) mapping....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1445
更新日期:1997-09-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv005
更新日期:2015-05-01 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::Amelogenesis imperfecta (AI) describes a broad group of clinically and genetically heterogeneous inherited defects of dental enamel bio-mineralization. Despite identification of a number of genetic mutations underlying AI, the precise causal mechanisms have yet to be determined. Using a multi-disciplinary approach, we...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq001
更新日期:2010-04-01 00:00:00
abstract::Mutations in DJ-1 cause recessively transmitted early-onset Parkinson disease (PD), and oxidative damage to DJ-1 has been associated with the pathogenesis of late-onset sporadic PD. The precise biochemical function of DJ-1 remains elusive. Here, we report that DJ-1 is synthesized as a latent protease zymogen with low-...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq113
更新日期:2010-06-15 00:00:00
abstract::Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddr270
更新日期:2011-09-15 00:00:00
abstract::The RIG-I-like receptors (RLRs)--RIG-I, IFIH1 (or MDA5) and LGP2--are thought to be key actors in the innate immune system, as they play a major role in sensing RNA viruses in the cytosol of host cells. Despite the increasingly recognized importance of the RLR family in antiviral immunity, no population genetic studie...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr377
更新日期:2011-11-15 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::Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies im...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu105
更新日期:2014-08-01 00:00:00
abstract::Development of neural circuitry depends on the integration of signaling pathways to coordinate specification, proliferation and differentiation of cell types in the right number, in the right place, at the right time. Zinc finger protein 423 (Zfp423), a 30-zinc finger transcription factor, forms alternate complexes wi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr300
更新日期:2011-10-01 00:00:00
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::Mutations of the novel renal glomerular genes NPHS1 and NPHS2 encoding nephrin and podocin cause two types of severe nephrotic syndrome presenting in early life, Finnish type congenital nephrotic syndrome (CNF) and a form of autosomal recessive familial focal segmental glomerulosclerosis (SRN1), respectively. To inves...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.4.379
更新日期:2002-02-15 00:00:00
abstract::Chromosomal aneuploidy, the gain or loss of whole chromosomes, is a hallmark of pathological conditions and a causal factor of birth defects and cancer. A number of studies indicate that aneuploid cells are present at a high frequency in the brain of mice and humans, suggesting that mosaic aneuploidies are compatible ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds375
更新日期:2012-12-15 00:00:00
abstract::In vertebrates, a proneural basic helix-loop-helix transcription factor (Ath5, Atonal homolog 5) plays a crucial role in the specification of the first retinal neuron: the retinal ganglion cell (RGC). Math5 homozygous null mutant mice lack RGCs and have no optic nerve. Furthermore, the expression of the Ath5 protein i...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/11.10.1207
更新日期:2002-05-15 00:00:00
abstract::TMEM70, a 21-kDa protein localized in the inner mitochondrial membrane, has been shown to facilitate the biogenesis of mammalian F1Fo ATP synthase. Mutations of the TMEM70 gene represent the most frequent cause of isolated ATP synthase deficiency resulting in a severe mitochondrial disease presenting as neonatal encep...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw295
更新日期:2016-11-01 00:00:00
abstract::Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri-Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of action, we have establ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.26.3083
更新日期:2001-12-15 00:00:00
abstract::The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identifi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg111
更新日期:2003-05-01 00:00:00
abstract::Friedreich's ataxia is a neurodegenerative disorder caused by mutations in the frataxin gene that produces a predominantly mitochondrial protein whose primary function appears to be mitochondrial iron-sulfur cluster (ISC) biosynthesis. Previously we demonstrated that frataxin interacts with multiple components of the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr582
更新日期:2012-04-01 00:00:00
abstract::Increasing evidence suggests that the accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria causes synaptic mitochondrial failure and synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was to better understand the effects of Aβ in mitochondrial activity and synaptic alterati...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr381
更新日期:2011-12-01 00:00:00
abstract::Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. To facilitate the identification of disease-causing mutations in the CPT II gene (CPT1), we have established the genomic organization of this gene. CPT1 spans approximately 20 kb of 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.1.19
更新日期:1995-01-01 00:00:00
abstract::Parental genetic relatedness may lead to adverse health and fitness outcomes in the offspring. However, the degree to which it affects human delivery timing is unknown. We use genotype data from ≃25 000 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study to optimize runs of homozygosity (RO...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa255
更新日期:2020-12-08 00:00:00
abstract::To further identify novel susceptibility loci of nasopharyngeal carcinoma (NPC), we here extended our previous genome-wide association study (GWAS) by boosting statistical power with larger sample size and validating more SNPs in the ranking list based on the GWAS P-values. The discovery stage consisting of 463,250 SN...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw200
更新日期:2016-08-15 00:00:00
abstract::Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusi...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddv270
更新日期:2015-10-15 00:00:00
abstract::CHARGE syndrome is a multiple congenital anomaly disorder that leads to life-threatening birth defects, such as choanal atresia and cardiac malformations as well as multiple sensory impairments, that affect hearing, vision, olfaction and balance. CHARGE is caused by heterozygous mutations in CHD7, which encodes an ATP...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt435
更新日期:2014-01-15 00:00:00
abstract::Peroxisome proliferator-activated receptors (PPARs) are ligand-mediated transcription factors, which control both lipid and energy metabolism and inflammation pathways. PPARγ agonists are effective in the treatment of metabolic diseases and, more recently, neurodegenerative diseases, in which they show promising neuro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds355
更新日期:2012-12-01 00:00:00
abstract::Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal reces...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr063
更新日期:2011-05-01 00:00:00
abstract::Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited malformation of the eye, which is characterized by microcornea with increased axial length, coloboma of the iris and of the optic disc, and severe myopia. We performed w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu744
更新日期:2015-04-15 00:00:00
abstract::Autosomal nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by mutations in the Aquaporin-2 (AQP2) gene. Analysis of a new family with dominant NDI revealed a single nucleotide deletion (727deltaG) in one AQP2 allele, which encoded ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.7.779
更新日期:2002-04-01 00:00:00