Title
Congenital hypomyelination in conjunction with de-novo mutation in the gene for the peripheral myelin protein 22 : the first confirmed case in the CR and review of the literature Congenital hypomyelination in conjunction with de-novo mutation in the gene for the peripheral myelin protein 22 : the first confirmed case in the CR and review of the literature
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Subject
Human medicine
Source (journal)
CESKA A SLOVENSKA NEUROLOGIE A NEUROCHIRURGIE
Volume/pages
65(2002) :3 , p. 206-212
ISSN
1210-7859
ISI
000176181300013
Carrier
E
Target language
English (eng)
Affiliation
University of Antwerp
Abstract
Congenital hypomyelination neuropathy (CHN) is the most severe form of Dejerine-Sottas neuropathy (DSN). Neuropathies of the Dejerine-Sottas (DSN or DSS) type are a severe form of hereditary peripheral neuropathy with a very early onset, relatively stable course and extremely reduced rate of conduction throught the peripheral nerve and extreme reduction of myelinized axons in combination with hypertrophic manifestations in the biopsy of the sural nerve. In patients with phenotype DSS and CHN so far mutations were found in genes MPZ, EGR2 and PMP22. Point mutations in PMP22 area relatively rare cause of hereditary motor-sensory neuropathies (HMSN), they were however found more frequently in patients with HMSN type III, who had healthy parents. Mutations in PMP22 develop often de novo and have a dominant effect. The authors describe the case of an 11-year-old boy, the offspring of healthy parents where from the neonatal period muscular hypotonia was observed and later marked retardation of the motor development only. The boy was so far unable to walk by himself. The intellect of the boy is markedly above the average. The neurological examination revealed marked muscular hypotonia and weakness and muscular hypotrophies. Tendinous muscular reflexes were markedly reduced or extinct. The motor rate of conduction through peripheral nerves was hardly detectable. In the biopsy of the sural nerve there was extreme demyelination to amyelination with absence of myelinated fibres combined with extensive hypertrophic manifestations of the type of onion bulb formations. The boy had no signs of affection of the CNS. At the age of 11 the clinical diagnosis of congenital hypomyelination was made, subsequent molecular genetic examination revealed in the patient a heterozygote mutation C on T in position 215 in the gene for PMP22, which causes the substitution of the amino acid serine for leucine. This mutation was not found in neither of the parents which made us conclude that it was a de novo dominant mutation. This mutation was already previously repeatedly described in sporadic cases with a similar CHN resp. DSS phenotype. Our finding supports previous theories on the so-called hot spot for mutations in gene PMP22. Patients with an extremely low rate of conduction through the peripheral nerve should be examined for the presence of mutations in gene PMP22.
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000176181300013&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000176181300013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle