Late Onset Type X mutations research from U of Padua

[Guest guest]

Research from J Peripher Nerv Syst. 2004 Jun;9(2):123.

A novel 9bp insertion in GJB1 gene causing late onset, intermediate CMT

in an italian patient.

Zortea M, Merlini L, Mostacciolo M.

Department of Biology, University of Padua, Italy.

Charcot-Marie-Tooth disease constitutes a clinically and genetically

heterogeneous group of hereditary motor and sensory peripheral

neuropathies. On the basis of electrophysiologic properties and

histopathology, CMT has been divided into demyelinating (type 1) and

axonal (type 2) neuropathies. The form of Charcot-Marie-Tooth neuropathy

that maps to Xq13 may present mild electrophysiological changes (NCV >

40 M/s), mixed neuropathy (NCV: Intermediate (30-40 M/s), or

demyelinating neuropathy (NCV: Slow (<37 M/s). On molecular grounds,

CMTX is caused by mutations in GJB1 gene, coding for Connexin 32

protein. A 42-year-old man, with no other affected family members, was

clinically evaluated for CMT. Three years ago he noticed thumb abductor

atrophy and then leg muscle atrophy. He presented with hand and leg

muscle atrophy, bilateral pes cavus, areflexia, and apallesthesia. The

median and ulnar motor NVC were 35-38 m/s, and the median sensory NVC

was 35 m/s. Both motor and sensory nerve action potentials were markedly

reduced. After exclusion of CMT1A and 1B, analysis for CMTX was

performed. The mutation screening of GJB1 gene showed a 9bp insertion

upstream the 194ATG codon (Met194) with preservation of the downstream

sequence. The three new amino acids (Thr-Val-Phe) inserted are localized

between the end of the second extracellular domain and the beginning of

the fourth transmembrane domain. This is the first 9bp insertion found

in GJB1 gene; a genotype-phenotype correlation may be deduced.