CMT Type 4 and variants research

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Abstract from Brain. 2004 Oct 6

Clinicopathological and genetic study of early-onset demyelinating

neuropathy.

Parman Y, Battaloglu E, Baris I, Bilir B, Poyraz M, Bissar-Tadmouri N,

A, Ammar N, Nelis E, Timmerman V, De Jonghe P, Necefov A,

Deymeer F, Serdaroglu P, Brophy PJ, Said G.

Department of Neurology, Istanbul University, Istanbul Medical Faculty,

Turkey.

Summary 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.