Mitochondrial GTPase mitofusin 2 mutation in Charcot?Marie?Tooth neuropathy type 2A
| Autor: | Yoshito Ishizaki, Yasunobu Shozawa, Chikahiko Numakura, Hiroko Izumino, Kazuki Kijima, Kiyoshi Hayasaka, Masafumi Ogawa, Toshihide Shiiki, Takeshi Kitamura, Atsuo Nezu, Kazuo Umetsu |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Heterozygote DNA Mutational Analysis MFN2 Mitochondrion Biology medicine.disease_cause GTP Phosphohydrolases Mitochondrial Proteins Mitofusin-2 Charcot-Marie-Tooth Disease Genetic linkage Genetics medicine Humans Child Gene Genetics (clinical) Mutation Membrane Proteins Chromosome Mitochondria mitochondrial fusion Child Preschool Female |
| Zdroj: | Human Genetics. 116:23-27 |
| ISSN: | 1432-1203 0340-6717 |
| DOI: | 10.1007/s00439-004-1199-2 |
| Popis: | Charcot-Marie-Tooth disease (CMT) has been classified into two types, CMT1 and CMT2, demyelinating and axonal forms, respectively. CMT2 has been further subdivided into eight groups by linkage studies. CMT2A is linked to chromosome 1p35-p36 and mutation in the kinesin family member 1B-beta (KIF1B) gene had been reported in one pedigree. However, no mutation in KIF1B was detected in other pedigrees with CMT2A and the mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) gene were recently detected in those pedigrees. MFN2, a mitochondrial transmembrane GTPase, regulates the mitochondrial network architecture by fusion of mitochondria. We studied MFN2 in 81 Japanese patients with axonal or unclassified CMT and detected seven mutations in seven unrelated patients. Six of them were novel and one of them was a de novo mutation. Most mutations locate within or immediately upstream of the GTPase domain or within two coiled-coil domains, which are critical for the functioning or mitochondrial targeting of MFN2. Formation of a mitochondrial network would be required to maintain the functional peripheral nerve axon. |
| Databáze: | OpenAIRE |
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