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A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis
Author(s) -
Thyagarajan Dominic,
Shanske Sara,
Vazquez Memije Marta,
Devivo Darryl,
Dimauro Salvatore
Publication year - 1995
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410380321
Subject(s) - heteroplasmy , proband , leigh disease , mitochondrial dna , mutation , point mutation , transition (genetics) , mitochondrion , biology , atpase , mutant , microbiology and biotechnology , adenosine triphosphate , genetics , gene , biochemistry , enzyme
A T‐to‐C transition at nucleotide (nt) 9176 in the mitochondrial adenosine triphosphatase 6 (ATPase 6) gene was detected in 2 brothers with a neurological disorder resembling Leigh syndrome. The mutation was also present in the 2 other siblings and in the mother, who were asymptomatic. In the more severely affected boy (the proband), the mutation was homoplasmic in muscle, leucocytes, and fibroblasts. In leucocytes from his affected brother, 98% of mtDNA was mutant. Heteroplasmy of varying degrees was seen in leucocytes from the mother and the 2 unaffected siblings. The mutation changes a highly conserved leucine residue near the carboxyl terminus of the mitochondrial ATPase 6 subunit to proline. It could not be detected in 168 control subjects. Studies of ATP synthesis and hydrolysis in fibroblasts from the proband were normal.