TY - JOUR
T1 - Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America
AU - Bassi, M.
AU - Bergen, Arthur
AU - Bitoun, Pierre
AU - Charles, Stephen
AU - Clementi, Maurizio
AU - Gosselin, Richard
AU - Hurst, Jane
AU - Lewis, Richard
AU - Lorenz, Birgit
AU - Meitinger, Thomas
AU - Messiaen, Ludwine
AU - Ramesar, Rajkumar
AU - Ballabio, Andrea
AU - Schiaffino, M.
N1 - Funding Information:
Acknowledgements We wish to thank Drs. John Yates and Gail Norbury for providing us with DNA samples from OA1 patients. This work was supported by a generous donation of the Vision of Children Foundation (San Diego, California), by the Italian Telethon Foundation, and by Research to Prevent Blindness, New York (R.A.L.). R.A.L. is a Senior Scientific Investigator of RPB.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=17744380598&partnerID=8YFLogxK
U2 - 10.1007/s004390000440
DO - 10.1007/s004390000440
M3 - Article
C2 - 11214907
AN - SCOPUS:17744380598
SN - 0340-6717
VL - 108
SP - 51
EP - 54
JO - Human Genetics
JF - Human Genetics
IS - 1
ER -