Article

Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America.

Telethon Institute of Genetics and Medicine, Milan, Italy.
Human Genetics (Impact Factor: 4.52). 02/2001; 108(1):51-4. DOI: 10.1007/s004390000440
Source: PubMed

ABSTRACT 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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    • "Additionally other types of " loss of function " mutations have been identified. Surprisingly, in approximately 30% of cases, no mutations were found (Schiaffino et al., 1995; Rosenberg and Schwartz, 1998; Bassi et al., 2001). Schnur et al. (1998) identified detectable alterations in OA1, including single bases mutations, in almost 90% of another set of patients analysed. "
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    • "Four different missense mutations were identified within i3 distally to the double-leucine in patients with ocular albinism, including G229V, T232K, E235K and I244V (Fig. 2A) (Schnur et al., 1998;Bassi et al., 2001). The role of these mutations in the pathogenesis of the disease remains to be established, since previous studies showed that in the context of the native OA1 they do not determine ER retention of the protein nor other apparent sorting defects (d'Addio et al., 2000;Shen et al., 2001). "
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