A first locus for isolated autosomal recessive optic atrophy (ROA1) maps to chromosome 8q.

Abstract

Abstract: : Purpose: To identify the disease causing gene in a large family affected with isolated recessive optic atrophy (ROA). Methods: A genome–wide search for homozygosity was performed in a large multiplex consanguineous family of French origin gathering four affected individuals, one healthy brother and both healthy parents. Results:Homozygosity was found for all four children on chromosome 8q allowing the localisation of the disease–causing gene to chromosome 8q21–q22 (Zmax of 3.41 at theta=0 for D8S270), in a 12 Mb interval flanked by markers D8S1702 and D8S1794. No other haploidentity was found in any other chromosomal region. Conclusions:In contrast to the frequent dominant optic atrophies (DOAs) in which the neuropathy is usually an isolated event, isolated recessive optic atrophies are very uncommon and have been described as severe congenital or early infantile conditions. To date, two loci for isolated DOA have been mapped, of which one was ascribed to mutations in the OPA1 gene. Here, we report the first mapping of a isolated autosomal ROA locus. This localisation excludes allelism of the disease with both isolated DOAs, on one hand, or all known syndromic forms of ROA, on the other hand.

Keywords: linkage analysis • gene mapping • neuro–ophthalmology: optic nerve