TY - JOUR
T1 - OA1 mutations and deletions in X-linked ocular albinism
AU - Schnur, Rhonda E.
AU - Gao, Mei
AU - Wick, Penelope A.
AU - Keller, Margaret
AU - Benke, Paul J.
AU - Edwards, Matthew J.
AU - Grix, Arthur W.
AU - Hockey, Athel
AU - Jung, Jack H.
AU - Kidd, Kenneth K.
AU - Kistenmacher, Mildred
AU - Levin, Alex V.
AU - Lewis, Richard A.
AU - Musarella, Maria A.
AU - Nowakowski, Rod W.
AU - Orlow, Seth J.
AU - Pagon, Roberta S.
AU - Pillers, De Ann M.
AU - Punnett, Hope H.
AU - Quinn, Graham E.
AU - Tezcan, Kamer
AU - Wagstaff, Joseph
AU - Weleber, Richard G.
N1 - Funding Information:
We thank Dr. N. Spinner for karyotype analysis of OAP-24, Dr. G. Murphy (University of Pennsylvania) for electron-microscopy analysis of the fetal skin sample, and Dr. P. Ray (Hospital for Sick Children) for performing computer-assisted laser densitometry of the dystrophin gene in OAP-26. Dr. L. Togi (Coriell Institute for Medical Research) kindly donated female control samples for polymorphism screening. This work was supported by a Clinical Research Award from the March of Dimes. During part of these studies, the work was supported by an Ethel Brown Foerderer Foundation for Excellence Fellowship (to R.E.S.); also, R.E.S. was a MAPS (Molecular Approaches to Pediatric Science) Scholar, supported by National Institutes of Health grant HD28815. R.A.L. is a Senior Scientific Investigator of Research to Prevent Blindness (New York). R.G.W. was supported by the Foundation Fighting Blindness, Inc., and by Research to Prevent Blindness (New York). M.A.M. was supported by the Atkinson Foundation, the Foundation Fighting Blindness, Inc., and the Retinitis Pigmentosa Research Foundation of Canada. D.M.P. was supported by the Foundation Fighting Blindness, Inc. and by National Institutes of Health grant EY10084.
PY - 1998/4
Y1 - 1998/4
N2 - X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity. Affected males usually demonstrate melanin macroglobules on skin biopsy. We now report results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian X-linked ocular albinism (OA) probands, including five with additional, nonocular phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2-8. Eight new missense mutations were identified, which cluster within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor-site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. In summary, 26 (~90%) of 29 probands had detectable alterations of OA1, thus confirming that OA1 is the major locus for X-linked OA.
AB - X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity. Affected males usually demonstrate melanin macroglobules on skin biopsy. We now report results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian X-linked ocular albinism (OA) probands, including five with additional, nonocular phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2-8. Eight new missense mutations were identified, which cluster within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor-site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. In summary, 26 (~90%) of 29 probands had detectable alterations of OA1, thus confirming that OA1 is the major locus for X-linked OA.
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U2 - 10.1086/301776
DO - 10.1086/301776
M3 - Article
C2 - 9529334
AN - SCOPUS:17344374015
SN - 0002-9297
VL - 62
SP - 800
EP - 809
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -