Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy.
The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.
Thompson
D A
DA
Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, USA. dathom@umich.edu
Li
Y
Y
McHenry
C L
CL
Carlson
T J
TJ
Ding
X
X
Sieving
P A
PA
Apfelstedt-Sylla
E
E
Gal
A
A
D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D017668:Age of Onset; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012162:Retinal Degeneration / Q000235:genetics*
D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase