Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNA ser(UCN) GENE
| Autor: | Antonio Toscano, Franco Carrara, Massimo Zeviani, Paolo Girlanda, Francesco Carella, Fiona M. Reid, Patrick Chariot, Paola Soliveri, Valeria Tiranti, Caterina Mariotti, Giovanni Matteo Fratta |
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| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Male
Myoclonus Mitochondrial DNA Ataxia Hearing loss Hearing Loss Sensorineural Mutant Molecular Sequence Data Mothers Base Sequence DNA Mitochondrial Female Humans Hybrid Cells Nucleic Acid Conformation Oxidative Phosphorylation Pedigree RNA Transfer Ser Syndrome Point Mutation Biology Sensorineural medicine.disease_cause Genetics medicine Hearing Loss Molecular Biology Genetics (clinical) Mutation Point mutation General Medicine DNA medicine.disease Heteroplasmy Mitochondrial Transfer Ser RNA Sensorineural hearing loss medicine.symptom |
| Popis: | We report on a new maternally-inherited syndrome characterized by a combination of sensorineural hearing loss, ataxia and myoclonus in a large kindred from Sicily. Hearing loss was the most widespread and sometimes the only symptom found in family members. Sequence analysis of the mitochondrial DNA regions encompassing the tRNA genes revealed the presence of a heteroplasmic insertion at nucleotide position 7472. The insertion adds a seventh cytosine to a six-cytosine run that is part of the mitochondrial tRNASer(UCN) gene. Conformational analysis showed that this mutation is likely to alter the structure of the T psi C loop in the tRNASer(UCN) clover leaf secondary structure. Moreover, the degree of heteroplasmy in blood and muscle was correlated with the clinical phenotype, and homoplasmic mutant hybrids showed decreased complex I activity, low oxygen consumption and high lactic acid output, indicating faulty oxidative phosphorylation. Finally, mutation was absent in 381 unrelated maternal lineages, suggesting specific segregation with the disease. We propose that the C7472 insertion-mutation is pathogenic, and etiologically related to hearing loss and other symptoms that define a novel maternally-inherited clinical entity. |
| Databáze: | OpenAIRE |
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