1. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 48
- Author
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Fabrizio Barbieri, Filippo M. Santorelli, Fiore Manganelli, F Pierelli, L. Santoro, and R Lanzillo
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Pathology ,medicine.medical_specialty ,Muscle biopsy ,Nerve biopsy ,medicine.diagnostic_test ,General Neuroscience ,Point mutation ,Cranial nerves ,Axonal loss ,Anatomy ,Gene mutation ,Biology ,medicine.disease ,medicine.anatomical_structure ,Mitochondrial myopathy ,medicine ,Neurology (clinical) ,Axon - Abstract
We describe two first cousins presenting a CMT phenotype associated with progressive external ophthalmoplegia (PEO) in one of them. The propositus (ML), a 37-year-old man, showed a severe muscular involvement both proximal and distal, bilateral ptosis, external ophthalmoplegia, hypophonia, bilateral pes cavus and absence of deep tendon reflexes (DTR). The cousin (MC), a 27-year-old man, showed a CMT phenotype with marked peroneal atrophy, pes cavus and absence of DTR. Cranial nerves were normal. Electrophysiological study revealed in the propositus, a severe axonal and demyelinating neuropathy and clear myopathic features at EMG. Accordingly, muscle biopsy showed both signs of mitochondrial myopathy and chronic denervation. Furthermore, nerve biopsy confirmed the severe axonal loss and showed abnormalities of myelin sheath which was thinner in relation to the axon diameter. In MC the electrophysiological study and the muscle and nerve biopsies showed only signs of a marked axonal neuropathy. Genetic analysis showed in the propositus a new homozygous mutation in POLG gene that encodes the mitochondrial DNA polymerase gamma. The same mutation was present in the heterozygous state in his parents and in MC. Moreover, the recent observation that mutations in GDAP1 gene could be associated with both axonal and demyelinating autosomal recessive CMT, prompted us to search for point mutations in this gene. However, the direct sequencing of GDAP1 gene did not show any mutation. In conclusion we describe two cousins presumably affected by an axonal autosomal recessive CMT. The presence in the propositus of the homozygous mutation of polymerase gamma gene adds to the CMT phenotype the myopathic features and PEO. It is questionable if in ML the axon hypomyelination could depend on the POLG gene mutation.
- Published
- 2003