Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa.
نویسندگان
چکیده
Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are the most common hereditary causes of visual impairment in infants and children. Using homozygosity mapping, we narrowed down the critical region of the LCA3 locus to 3.8 Mb between markers D14S1022 and D14S1005. By direct Sanger sequencing of all genes within this region, we found a homozygous nonsense mutation in the SPATA7 gene in Saudi Arabian family KKESH-060. Three other loss-of-function mutations were subsequently discovered in patients with LCA or juvenile RP from distinct populations. Furthermore, we determined that Spata7 is expressed in the mature mouse retina. Our findings reveal another human visual-disease gene that causes LCA and juvenile RP.
منابع مشابه
Novel homozygous large deletion including the 5′ part of the SPATA7 gene in a consanguineous Israeli Muslim Arab family
PURPOSE To identify the genetic defect in a consanguineous Israeli Muslim Arab family with juvenile retinitis pigmentosa (RP). METHODS DNA samples were collected from the index patient, her parents, her affected sister, and two non-affected siblings. Genome-wide linkage analysis with 250 K single nucleotide polymorphism (SNP) arrays was performed using DNA from the two affected patients. Owin...
متن کاملSpata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and protein trafficking in the retina.
Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are severe hereditary diseases that causes visual impairment in infants and children. SPATA7 has recently been identified as the LCA3 and juvenile RP gene in humans, whose function in the retina remains elusive. Here, we show that SPATA7 localizes at the primary cilium of cells and at the connecting cilium (CC) of photorece...
متن کاملLow prevalence of LRAT mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa
PURPOSE To determine the the prevalence of pathogenic mutations in the gene encoding lecithin retinol acyltransferase (LRAT) in patients from North America with either Leber congenital amaurosis (LCA) or autosomal recessive retinitis pigmentosa (ARRP). METHODS Exon 1, exon 2, and the coding region of exon 3 of LRAT were PCR-amplified and directly sequenced from the leukocyte DNA of 82 unrelat...
متن کاملComprehensive molecular diagnosis of 179 Leber congenital amaurosis and juvenile retinitis pigmentosa patients by targeted next generation sequencing.
BACKGROUND Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are inherited retinal diseases that cause early onset severe visual impairment. An accurate molecular diagnosis can refine the clinical diagnosis and allow gene specific treatments. METHODS We developed a capture panel that enriches the exonic DNA of 163 known retinal disease genes. Using this panel, we perform...
متن کاملHomozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families
Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in ...
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ورودعنوان ژورنال:
- American journal of human genetics
دوره 84 3 شماره
صفحات -
تاریخ انتشار 2009