TY - JOUR
T1 - Mitochondrial neurogastrointestinal encephalomyopathy syndrome maps to chromosome 22q13.32-qter
AU - Hirano, Michio
AU - Garcia-de-Yebenes, Justo
AU - Jones, Alison C.
AU - Nishino, Ichizo
AU - DiMauro, Salvatore
AU - Carlo, José R.
AU - Bender, Adam N.
AU - Hahn, Angelica F.
AU - Salberg, Larry M.
AU - Weeks, Daniel E.
AU - Nygaard, Torbjoern G.
N1 - Funding Information:
The authors thank the families who cooperated with this study, Drs. Hong Shen and Caiping Chen for technical assistance, and Dr. Hiroshi Mitsumoto for his kind assistance with family 2. The study was supported by National Institutes of Health (NIH) grants K08-NS01617 and RO1-HL59657 (to M.H.), NS32035 (to T.G.N.), and RR11126 (to J.R.C.); the Columbia-Presbyterian Irving Scholars Program (support to M.H.); and the University of Pittsburgh and The Wellcome Trust Centre for Human Genetics (support to D.E.W.).
PY - 1998/8
Y1 - 1998/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032231702&partnerID=8YFLogxK
U2 - 10.1086/301979
DO - 10.1086/301979
M3 - Article
AN - SCOPUS:0032231702
SN - 0002-9297
VL - 63
SP - 526
EP - 533
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -