GENOTYPE TO PHENOTYPE CORRELATIONS IN MITOCHONDRIAL ENCEPHALOMYOPATHIES ASSOCIATED WITH THE A3243G MUTATION OF MITOCHONDRIAL-DNA

被引：88

作者：

MARIOTTI, C

SAVARESE, N

SUOMALAINEN, A

RIMOLDI, M

COMI, G

PRELLE, A

ANTOZZI, C

SERVIDEI, S

JARRE, L

DIDONATO, S

ZEVIANI, M

机构：

[1] IST NAZL NEUROL CARLO BESTA,DIV BIOCHIM & GENET,I-20133 MILAN,ITALY

[2] UNIV STATALE MILAN,CTR DINO FERRARI,IST CLIN NEUROL,MILAN,ITALY

[3] UNIV STATALE TURIN,NEUROPSICHIATRIA INFANTILE CLIN,TURIN,ITALY

[4] UNIV CATTOLICA,NEUROL CLIN,ROME,ITALY

[5] NATL PUBL HLTH INST,DEPT HUMAN MOLEC GENET,HELSINKI,FINLAND

来源：

JOURNAL OF NEUROLOGY | 1995年 / 242卷 / 05期

关键词：

MITOCHONDRIAL ENCEPHALOMYOPATHY; CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; LACTIC ACIDOSIS; STROKE-LIKE EPISODES; RAGGED-RED FIBERS;

D O I：

10.1007/BF00878873

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods: densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex I, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly cor related with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS(3243) and CPEO(3243) we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNA(Leu(UUR)) gene.

引用

页码：304 / 312

页数：9

共 26 条

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