Type 1C sciatic nerve cell research

[Guest guest]

Research from Ann Neurol. 2004 May;55(5):713-720.

SIMPLE mutation in demyelinating neuropathy and distribution in sciatic

nerve.

CL, Shirk AJ, Huynh HM, Street VA, Nelis E, Van Maldergem L, De

Jonghe P, Jordanova A, Guergueltcheva V, Tournev I, Van Den Bergh P,

Seeman P, Mazanec R, Prochazka T, Kremensky I, Haberlova J, Weiss MD,

Timmerman V, Bird TD, Chance PF.

Department of Pediatrics, Division of Genetics and Developmental

Medicine, University of Washington, Seattle, WA.

Charcot-Marie-Tooth neuropathy type 1C (CMT1C) is an autosomal dominant

demyelinating peripheral neuropathy caused by missense mutations in the

small integral membrane protein of lysosome/late endosome (SIMPLE) gene.

To investigate the prevalence of SIMPLE mutations, we screened a cohort

of 152 probands with various types of demyelinating or axonal and pure

motor or sensory inherited neuropathies. SIMPLE mutations were found

only in CMT1 patients, including one G112S and one W116G missense

mutations. A novel I74I polymorphism was identified, yet no splicing

defect of SIMPLE is likely. Haplotype analysis of STR markers and

intragenic SNPs linked to the gene demonstrated that families with the

same mutation are unlikely to be related. The clustering of the G112S,

T115N, and W116G mutations within five amino acids suggests this domain

may be critical to peripheral nerve myelination. Electrophysiological

studies showed that CMT1C patients from six pedigrees (n = 38) had

reduced nerve conduction velocities ranging from 7.5 to 27.0m/sec

(peroneal). Two patients had temporal dispersion of nerve conduction and

irregularity of conduction slowing, which is unusual for CMT1 patients.

We report the expression of SIMPLE in various cell types of the sciatic

nerve, including Schwann cells, the affected cell type in CMT1C.