MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY SYNDROME MAPS TO CHROMOSOME 22Q13.32-QTER

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare, multisystem disorder characterized clinically by ptosis, p rogressive external ophthalmoplegia, gastrointestinal dysmotility, leu koencephalopathy, thin body habitus, and myopathy. Laboratory studies reveal defects of oxidative-phosphorylation and multiple mtDNA deletio ns frequently in skeletal muscle. We studied four ethnically distinct families affected with this apparently autosomal recessive disorder. P robands from each family were shown, by Southern blot, to have multipl e mtDNA deletions in skeletal muscle. We mapped the MNGIE locus to 22q 13.32-qter, distal to D22S1161, with a maximum two-point LOD score of 6.80 at locus D22S526. Cosegregation of MNGIE with a single chromosoma l region in families with diverse ethnic backgrounds suggests that we have mapped an important locus for this disorder. We found no evidence to implicate three candidate genes in this region, by using direct se quence analysis for DNA helicase Il and by assaying enzyme activities for arylsulfatase A and carnitine palmitoyltransferase.