Screening genes of the retinoid metabolism: novel LRAT mutation in leber congenital amaurosis.
OBJECTIVE
To evaluate the mutation prevalence and phenotype in genes involved in the ocular retinoid metabolism.


METHODS
We analyzed LRAT, encoding the lecithin retinol acyltransferase, and RDH10, a retinal pigment epithelium-specific retinol dehydrogenase.


METHODS
We screened by denaturing-high performance liquid chromatography (D-HPLC) and direct sequencing all coding exons of LRAT and RDH10 in 216 patients, including 134 with simplex or multiplex retinitis pigmentosa and 82 with various types of flecked retinal dystrophies.


RESULTS
Only nonpathogenic variants were found in this series. In an additional 2.5-year-old patient presenting with an "RPE65" phenotype (night blindness, photoattractivity, and visual improvement several months after birth), we discovered a homozygous deletion in LRAT (c.217_218delAT) leading to a premature stop at codon 120.


CONCLUSIONS
The phenotype of patients with mutations in LRAT is similar to that of patients with mutations in RPE65, suggesting the need to systematically screen both genes in case of typical phenotype.
Sénéchal
Audrey
A
Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier, Hôpital Saint-Eloi, Montpellier Cedex 5, France.
Humbert
Ghyslaine
G
Surget
Marie-Odile
MO
Bazalgette
Cécile
C
Bazalgette
Christian
C
Arnaud
Bernard
B
Arndt
Carl
C
Laurent
Eric
E
Brabet
Philippe
P
Hamel
Christian P
CP
D000217:Acyltransferases / Q000235:genetics*; D000429:Alcohol Oxidoreductases / Q000235:genetics; D001766:Blindness / Q000151:congenital* / Q000235:genetics*; D002352:Carrier Proteins; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D016368:Frameshift Mutation; D005820:Genetic Testing; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics; D012176:Retinoids / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D000217:Acyltransferases; D000429:Alcohol Oxidoreductases; D002352:Carrier Proteins; D005136:Eye Proteins; D012176:Retinoids; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C113992:trans-retinol dehydrogenase; C056942:lecithin-retinol acyltransferase