Mutations in the UBIAD1 gene, encoding a potential prenyltransferase, are causal for Schnyder crystalline corneal dystrophy.
Schnyder crystalline corneal dystrophy (SCCD, MIM 121800) is a rare autosomal dominant disease characterized by progressive opacification of the cornea resulting from the local accumulation of lipids, and associated in some cases with systemic dyslipidemia. Although previous studies of the genetics of SCCD have localized the defective gene to a 1.58 Mbp interval on chromosome 1p, exhaustive sequencing of positional candidate genes has thus far failed to reveal causal mutations. We have ascertained a large multigenerational family in Nova Scotia affected with SCCD in which we have confirmed linkage to the same general area of chromosome 1. Intensive fine mapping in our family revealed a 1.3 Mbp candidate interval overlapping that previously reported. Sequencing of genes in our interval led to the identification of five putative causal mutations in gene UBIAD1, in our family as well as in four other small families of various geographic origins. UBIAD1 encodes a potential prenyltransferase, and is reported to interact physically with apolipoprotein E. UBIAD1 may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage.
Orr
Andrew
A
Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.
Dubé
Marie-Pierre
MP
Marcadier
Julien
J
Jiang
Haiyan
H
Federico
Antonio
A
George
Stanley
S
Seamone
Christopher
C
Andrews
David
D
Dubord
Paul
P
Holland
Simon
S
Provost
Sylvie
S
Mongrain
Vanessa
V
Evans
Susan
S
Higgins
Brent
B
Bowman
Sharen
S
Guernsey
Duane
D
Samuels
Mark
M
D000595:Amino Acid Sequence; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002874:Chromosome Mapping; D019295:Computational Biology; D003315:Cornea / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000201:enzymology / Q000235:genetics; D004252:DNA Mutational Analysis; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009674:Nova Scotia; D010375:Pedigree; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment
D011506:Proteins; D002784:Cholesterol; D004122:Dimethylallyltranstransferase; C425464:UBIAD1 protein, human