Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenitalamaurosis

Citation
Mm. Sohocki et al., Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenitalamaurosis, NAT GENET, 24(1), 2000, pp. 79-83
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
1061-4036 → ACNP
Volume
24
Issue
1
Year of publication
2000
Pages
79 - 83
Database
ISI
SICI code
1061-4036(200001)24:1<79:MIANPG>2.0.ZU;2-U
Abstract
Leber congenital amaurosis (LCA, MIM 204000) accounts for at least 5% of al l inherited retinal disease(1) and is the most severe inherited retinopathy with the earliest age of onset(2). Individuals affected with LCA are diagn osed at birth or in the first few months of life with severely impaired vis ion or blindness, nystagmus and an abnormal or flat electroretinogram (ERG) . Mutations in GUCY2D (ref. 3), RPE65 (ref. 4) and CRX (ref. 5) are known t o cause LCA, but one study identified disease-causing GUCY2D mutations in o nly 8 of 15 families whose LCA locus maps to 17p13.1 (ref. 3), suggesting a nother LCA locus might be located on 17p13.1. Confirming this prediction, t he LCA in one Pakistani family mapped to 17p13.1, between D17S849 and D17S9 60-a region that excludes GUCY2D. The LCA in this family has been designate d LCA4 (ref. 6). We describe here a new photoreceptor/pineal-expressed gene , AIPL1 (encoding aryl-hydrocarbon interacting protein-like 1), that maps w ithin the LCA4 candidate region and whose protein contains three tetratrico peptide (TPR) motifs, consistent with nuclear transport or chaperone activi ty. A homozygous nonsense mutation at codon 278 is present in all affected members of the original LCA4 family. AIPL1 mutations may cause approximatel y 20% of recessive LCA, as disease-causing mutations were identified in 3 o f 14 LCA families not tested previously for linkage.