Mitochondrial neurogastrointestinal encephalomyopathy syndrome maps to chromosome 22q13.32-qter.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare, multisystem disorder characterized clinically by ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility, leukoencephalopathy, thin body habitus, and myopathy. Laboratory studies reveal defects of oxidative-phosphorylation and multiple mtDNA deletions frequently in skeletal muscle. We studied four ethnically distinct families affected with this apparently autosomal recessive disorder. Probands from each family were shown, by Southern blot, to have multiple mtDNA deletions in skeletal muscle. We mapped the MNGIE locus to 22q13.32-qter, distal to D22S1161, with a maximum two-point LOD score of 6.80 at locus D22S526. Cosegregation of MNGIE with a single chromosomal 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 sequence analysis for DNA helicase II and by assaying enzyme activities for arylsulfatase A and carnitine palmitoyltransferase.
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. mh29@columbia.edu
M
M
Hirano
J
J
Garcia-de-Yebenes
A C
AC
Jones
I
I
Nishino
S
S
DiMauro
J R
JR
Carlo
A N
AN
Bender
A F
AF
Hahn
L M
LM
Salberg
D E
DE
Weeks
T G
TG
Nygaard
D000293:Adolescent; D000328:Adult; D001763:Blepharoptosis / Q000235:genetics; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D004272:DNA, Mitochondrial / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009886:Ophthalmoplegia / Q000235:genetics; D010085:Oxidative Phosphorylation; D010375:Pedigree; D017384:Sequence Deletion; D013577:Syndrome
D004272:DNA, Mitochondrial; D005819:Genetic Markers