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 condition ch aracterized by infantile optic atrophy, an early onset movement disord er, and 3-methylglutaconic aciduria, Other features include spastic pa raplegia, mild ataxia, mild cognitive deficiency and dysarthria. This disorder was identified in inbred Iraqi-Jewish kindreds in which relat ionships between most of the affected individuals were unknown, In thi s study we identify linkage to chromosome 19q13.2-q13.3 by using a DNA pooling strategy to perform a genome wide screen followed by a high d ensity search for shared segments among affected individuals in candid ate regions identified in the initial genome wide screen, A significan tly high positive lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3' untranslated region of the myotonic dyst rophy protein kinase gene, The existence of multiple recombinant indiv iduals indicates the disease interval can be further narrowed with add itional markers, Linkage disequilibrium was seen in six polymorphic ma rkers across al Mb interval, This region is well characterized and con tains several candidate genes.