Report of a novel mutation in CRB1 in a Lebanese family presenting retinal dystrophy.
OBJECTIVE
To identify the genetic basis of a recessive inheritance form of retinal dystrophy (RD) in a Lebanese family.


METHODS
Clinical data were recorded for five patients of the 14 family members. Genetic linkage was carried out using Affymetrix 250 K Nspl SNP array followed by sequencing.


RESULTS
The patients showed variable phenotypes ranging from Leber Congenital Amaurosis (LCA) to progressive forms of Retinitis Pigmentosa (RP). A 46.1 Mb chromosomal region at chromosome 1q23.3-32.2 was identified by homozygosity mapping. This region contained the Crumbs homologue-1, CRB1, a gene responsible for recessive retinal dystrophies. CRB1 is required for photoreceptor morphogenesis, and it has been associated with RP and LCA. Sequencing of CRB1 revealed two mutations: a novel deletion in exon 6 (c.1772_1775delGCAT; p.C591Sfs*28) and a missense mutation in exon 7 (c.2234C > T; p.T745M).


CONCLUSIONS
We report a novel CRB1 mutation in inherited RD in a Lebanese family, and confirm the considerable phenotype heterogeneity that may exist between individuals sharing the same mutations.
Unité de Génétique Médicale et laboratoire associé INSERM à l'Unité UMR_S 910. Pôle Technologie Santé, Université Saint-Joseph , Beirut , Lebanon , and.
Nadine
N
Jalkh
Claire
C
Guissart
Eliane
E
Chouery
Tony
T
Yammine
Nagham
N
El Ali
Hanane Abi
HA
Farah
André
A
Mégarbané
D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D008040:Genetic Linkage; D006801:Humans; D007861:Lebanon; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D058499:Retinal Dystrophies / Q000175:diagnosis / Q000235:genetics*; D017384:Sequence Deletion
C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins