共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Wenmin Sun Xueshan Xiao Shiqiang Li Jiamin Ouyang Xueqing Li Xiaoyun Jia Xing Liu Qingjiong Zhang 《遗传学报》2019,(7)
<正>Primary angle closure glaucoma(PACG)is one of the most common causes of irreversible blindness in Asia and about 80%of PACG are present in Asia(Song et al.,2017).Genetics plays an important role in the development of PACG(Gramer et al.,2014).Recently,eight common SNPs were found to be strongly associated with PACG(Vithana et al.,2012;Khor et al.,2016)and mutations in MYRF cause high hyperopia accompanied with PACG(Xiao et al.,2019).However,the genetic defects underlying PACG are still 相似文献
3.
4.
5.
Retinitis pigmentosa (RP) is a genetically heterogeneous disease and an important cause of blindness in the state of Andhra
Pradesh in India. In an attempt to identify the disease locus in families with the recessive form of the disease, we used
the approach of screening for homozygosity by descent in offspring of consanguineous and nonconsanguineous families with RP.
Microsatellite markers closely flanking 21 known candidate genes for RP were genotyped in parents and affected offspring to
determine whether there was homozygosity at these loci that was shared by affected individuals of a family. This screening
approach may be a rapid preliminary method to test known loci for possible cosegregation with disease. 相似文献
6.
Hanan E. Shamseldin Maha Tulbah Wesam Kurdi Maha Nemer Nada Alsahan Elham Al Mardawi Ola Khalifa Amal Hashem Ahmed Kurdi Zainab Babay Dalal K. Bubshait Niema Ibrahim Firdous Abdulwahab Zuhair Rahbeeni Mais Hashem Fowzan S. Alkuraya 《Genome biology》2015,16(1)
BackgroundIdentifying genetic variants that lead to discernible phenotypes is the core of Mendelian genetics. An approach that considers embryonic lethality as a bona fide Mendelian phenotype has the potential to reveal novel genetic causes, which will further our understanding of early human development at a molecular level. Consanguineous families in which embryonic lethality segregates as a recessive Mendelian phenotype offer a unique opportunity for high throughput novel gene discovery as has been established for other recessive postnatal phenotypes.ResultsWe have studied 24 eligible families using autozygosity mapping and whole-exome sequencing. In addition to revealing mutations in genes previously linked to embryonic lethality in severe cases, our approach revealed seven novel candidate genes (THSD1, PIGC, UBN1, MYOM1, DNAH14, GALNT14, and FZD6). A founder mutation in one of these genes, THSD1, which has been linked to vascular permeability, accounted for embryonic lethality in three of the study families. Unlike the other six candidate genes, we were able to identify a second mutation in THSD1 in a family with a less severe phenotype consisting of hydrops fetalis and persistent postnatal edema, which provides further support for the proposed link between this gene and embryonic lethality.ConclusionsOur study represents an important step towards the systematic analysis of “embryonic lethal genes” in humans.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0681-6) contains supplementary material, which is available to authorized users. 相似文献7.
Züchner S Dallman J Wen R Beecham G Naj A Farooq A Kohli MA Whitehead PL Hulme W Konidari I Edwards YJ Cai G Peter I Seo D Buxbaum JD Haines JL Blanton S Young J Alfonso E Vance JM Lam BL Peričak-Vance MA 《American journal of human genetics》2011,(2):581-206
Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions. 相似文献
8.
9.
10.
Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular retinal pigment epithelium atrophy
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Chakarova CF Papaioannou MG Khanna H Lopez I Waseem N Shah A Theis T Friedman J Maubaret C Bujakowska K Veraitch B Abd El-Aziz MM Prescott de Q Parapuram SK Bickmore WA Munro PM Gal A Hamel CP Marigo V Ponting CP Wissinger B Zrenner E Matter K Swaroop A Koenekoop RK Bhattacharya SS 《American journal of human genetics》2007,81(5):1098-1103
We report mutations in the gene for topoisomerase I-binding RS protein (TOPORS) in patients with autosomal dominant retinitis pigmentosa (adRP) linked to chromosome 9p21.1 (locus RP31). A positional-cloning approach, together with the use of bioinformatics, identified TOPORS (comprising three exons and encoding a protein of 1,045 aa) as the gene responsible for adRP. Mutations that include an insertion and a deletion have been identified in two adRP-affected families--one French Canadian and one German family, respectively. Interestingly, a distinct phenotype is noted at the earlier stages of the disease, with an unusual perivascular cuff of retinal pigment epithelium atrophy, which was found surrounding the superior and inferior arcades in the retina. TOPORS is a RING domain-containing E3 ubiquitin ligase and localizes in the nucleus in speckled loci that are associated with promyelocytic leukemia bodies. The ubiquitous nature of TOPORS expression and a lack of mutant protein in patients are highly suggestive of haploinsufficiency, rather than a dominant negative effect, as the molecular mechanism of the disease and make rescue of the clinical phenotype amenable to somatic gene therapy. 相似文献
11.
I. Zito D.L. Thiselton M.B. Gorin J.T. Stout C. Plant A.C. Bird S.S. Bhattacharya A.J. Hardcastle 《Human genetics》1999,105(1-2):57-62
The X-linked form of retinitis pigmentosa (XLRP) is a severe disease of the retina, characterised by night blindness and
visual field constriction in a degenerative process, culminating with complete loss of sight within the third decade of life.
Genetic mapping studies have identified two major loci for XLRP: RP3 (70%–75% of XLRP) and RP2 (20%–25% of XLRP). The RPGR (retinitis pigmentosa GTPase regulator) gene has been cloned within the RP3 genomic interval and it has been shown that 10%–20%
of XLRP families have mutations in this gene. Here, we describe a single-strand conformational polymorphism-based mutation
screening of RPGR in a pool of 29 XLRP families for which the disease segregates with the RP3 locus, in order to investigate the proportion of RP3 families with RPGR mutations and to relate the results to previous reports. Five different new mutations have been identified: two splice site
mutations for exon 1 and three frameshift mutations in exons 7, 10 and 11. The percentage of RPGR mutations identified is 17% (5/29) in our genetically well-defined population. This figure is comparable to the percentage
of RP2 gene mutations that we have detected in our entire XLRP patient pool (10%–15%). A correlation of RPGR mutations with phenotype in the families described in this study and the biochemical characterisation of reported mutations
may provide insights into the function of the protein.
Electronic Publication 相似文献
12.
Multipoint linkage analysis and heterogeneity testing in 20 X-linked retinitis pigmentosa families 总被引:6,自引:0,他引:6
M A Musarella L Anson-Cartwright S M Leal L D Gilbert R G Worton G A Fishman J Ott 《Genomics》1990,8(2):286-296
Using multipoint linkage analysis in 20 families segregating for X-linked retinitis pigmentosa (XLRP), the lod scores on a map of eight RFLP loci were obtained. Our results indicate that under the hypothesis of homogeneity the maximal multipoint lod score supports one disease locus located slightly distal to OTC at Xp21.1. Heterogeneity testing for two XLRP loci suggested that a second XLRP locus may be located 8.5 cM proximal to DXS28 at Xp21.3. Further heterogeneity testing for three disease loci failed to detect a third XLRP locus proximal to DXS7 in any of our 20 XLRP families. 相似文献
13.
14.
PAP-1 has been identified by us as a Pim-1-binding protein and has recently been implicated as the defective gene in RP9, one type of autosomal dominant retinitis pigmentosa (adRP). We have then shown that PAP-1 plays a role in pre-mRNA splicing. Because four causative genes for adRP, including PAP-1, Prp31, Prp8, and Prp3, encode proteins that function as splicing factors or splicing-modulating factors, we investigated the interaction of PAP-1 with Prp3p and Prp31p in this study. The results showed that PAP-1 interacted with Prp3p but not Prp31p in human cells and yeast, and that the basic region of PAP-1 and the C-terminal region of Prp3p, regions beside spots found in adRP mutations, were needed for binding. Furthermore, both Prp3p and a part of PAP-1 were found to be components of the U4/U6.U5-tri-snRNP complex, one form of the spliceosome, in Ba/F3 and K562 cells by analysis of sucrose density gradients, suggesting that PAP-1 is weakly associated with the spliceosome. These results also suggest that splicing factors implicated in adRP contribute alone or mutually to proper splicing in the retina and that loss of their functions leads to onset of adRP. 相似文献
15.
Mónica Bayés Diana Valverde Susana Balcells Daniel Grinberg Lluïsa Vilageliu Javier Benítez Carmen Ayuso Magdalena Beneyto Montserrat Baiget Roser Gonzàlez-Duarte 《Human genetics》1995,96(1):89-94
Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the genes encoding rhodopsin, the subunit of rod phosphodiesterase (PDEB) and, recently, in the gene for rod cGMP-gated channel, have been reported. However, detailed genetic involvement has not been ascertained in the great majority of cases. Recoverin, another member of the light transduction pathway, is a candidate gene for ARRP. We report the first analyses of the involvement of the recoverin gene (RCV1) in 42 Spanish ARRP families. Linkage and homozygosity studies with an intragenic polymorphism and the close markers D17S945 and D17S786 ruled out RCV1 as the cause of ARRP in 38 pedigrees. In the four remaining families, single strand conformation polymorphism analysis of the recoverin-coding region detected no mutations in the parents or in the affected members. These results strongly suggest that mutations in the RCV1 gene are not responsible for ARRP in these families. 相似文献
16.
Wang Y Guo L Cai SP Dai M Yang Q Yu W Yan N Zhou X Fu J Guo X Han P Wang J Liu X 《PloS one》2012,7(5):e33673
Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family. 相似文献
17.
18.
González-del Pozo M Borrego S Barragán I Pieras JI Santoyo J Matamala N Naranjo B Dopazo J Antiñolo G 《PloS one》2011,6(12):e27894
Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing. 相似文献
19.
20.
Oscar F. Chacon-Camacho Serguei Jitskii Beatriz Buentello-Volante Jonathan Quevedo-Martinez Juan C. Zenteno 《Gene》2013