oa Identification and Mapping of Locus on the Long Arm of Chromosome 4 that is Associated with Mental Retardation and Optic Atrophy in a Qatari Aamily with Undelineated Autosomal Recessive Disease

Background: Autosomal recessive diseases are the single largest category of single-gene disorders among Arab population. A Qatari family includes 6 individuals from 3 related consanguineous sibships, with mental retardation. The clinical picture comprised significant mental retardation, retinal degeneration, optic nerve atrophy, and ataxic gait. They suffer also from oedemal puffiness of hands and feet. All parents and the unaffected family members are healthy.

Objective: Identification of undelineated autosomal recessive disorders among families in the Arab world, especially in the Gulf region.

Methods: Whole genome genotyping was done by (Illumina 300Kb SNPs), followed by homozygosity mapping and linkage analysis. Targeted resequencing of candidate genes was preformed within the linked loci.

Results and conclusions: Homozygosity mapping revealed a 19.6 MB segment in the long arm of chromosome 4 flanked by rs4345237 (4q12) and rs422140 (4q13.3). This interval contains more than 100 genes, none of which has been implicated in any of the above mentioned phenotype so far. Candidate genes were selected and we are in the process of sequencing them. In addition, whole exome sequencing will be performed to expedite the mutation identification.