Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene

Iraqi-Jewish optic atrophy plus is an autosomal recessive conditioncharacterized by infantile optic atrophy, an early onset movement disorder,and 3-methylglutaconic aciduria. Other features include spastic paraplegia,mild ataxia, mild cognitive deficiency and dysarthria. This disorder wasidentified in inbred Iraqi-Jewish kindreds in which relationships betweenmost of the affected individuals were unknown. In this study we identifylinkage to chromosome 19q13.2-q13.3 by using a DNA pooling strategy toperform a genome wide screen followed by a high density search for sharedsegments among affected individuals in candidate regions identified in theinitial genome wide screen. A significantly high positive lod score of 6.14at zero recombination was obtained for the CTG repeat in the 3'untranslated region of the myotonic dystrophy protein kinase gene. Theexistence of multiple recombinant individuals indicates the diseaseinterval can be further narrowed with additional markers. Linkagedisequilibrium was seen in six polymorphic markers across a 1 Mb interval.This region is well characterized and contains several candidate genes.