Brain Advance Access originally published online on October 6, 2004
Brain 2004 127(11):2540-2550; doi:10.1093/brain/awh275
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Brain Vol. 127 No. 11 © Guarantors of Brain 2004; all rights reserved
Clinicopathological and genetic study of early-onset demyelinating neuropathy
im Parman1,*
lu2,*
2lu1
1 Department of Neurology, Istanbul University, Istanbul Medical Faculty, 2 Department of Molecular Biology and Genetics, Boaziçi University, Istanbul, Turkey, 3 Department of Preclinical Veterinary Sciences, University of Edinburgh, Edinburgh, UK, 4 Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium and 5 Department of Neurology, Centre Hospitalier Universitaire de Bicetre, Paris, France
Correspondence to: Yesim Parman, Department of Neurology, Istanbul Medical Faculty, Istanbul University, Millet Cad., Capa, 34390 Istanbul, Turkey E-mail: parman{at}tnn.net
Autosomal recessive demyelinating Charcot–Marie–Tooth disease (CMT4), Dejerine–Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene.
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