Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.
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PMID:Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America. 1121 7

X-linked ocular albinism type 1 (OA1) is caused by mutations in G protein-coupled receptor 143 (GPR143) gene, which encodes a membrane glycoprotein localized to melanosomes. GPR143 mainly affects pigment production in the eye, resulting in optic changes associated with albinism, including hypopigmentation of the retina, nystagmus, strabismus, foveal hypoplasia, abnormal crossing of the optic fibers, and reduced visual acuity. We report the mutational analysis of the GPR143 gene on two unrelated families with OA1 using direct sequencing and real-time quantitative polymerase chain reaction. We identified the c.564_565delCT, a 2-bp deletion in family 1, and we mapped the breakpoints at nucleotide level of the novel intragenic deletion g.5360_6371del1012, encompassing exon 2, in family 2. Our results confirm that GPR143 is the major locus for OA1 and that exon 2 is a region of high susceptibility to deletions. Finally, we emphasize the quantitative polymerase chain reaction as a valid tool for diagnosis of deletions in the GPR143 gene.
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PMID:GPR143 mutational analysis in two Italian families with X-linked ocular albinism. 1960 13