Klinik und Molekulargenetik der hereditären motorischen und sensiblen Neuropathien im Kindesalter

Hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth (CMT) disease comprises a group of clinically and genetically heterogeneous disorders of the peripheral nervous system. With an overall prevalence of 1 in 2500, CMT is the most common inherited neuromuscular disorder in man. This study points out the variety of responsible mutations of patients with early childhood onset HSMN and draws a better understanding of the structure and function of the proteins, which are liable for the peripheral nervous system. It can be confirmed that new autosomal dominant mutations play a vital role in the differential diagnosis of sporadically HMSN cases. If the expression of the clinical features differs within one family from mild affected female to severe affected male especially Cx32-mutations have to be taken into account. In this study, two novel GDAP1-mutations are demonstrated, which probably lead to a shortened and dysfunctional protein. This mutations cause intermediate i.e. axonal as well as demyelinating neuropathies. By genotyping of two families the number of suitable loci could be minimized and consequently lead to the identification of new HSMN-genes in later studies. Correlations between genotype and phenotype are currently possible to a limited extent only. Certain clinical and histopathological indicators draw suspicion to certain genes. E.g. a severe scoliosis points to the CMT4C-locus (KIAA1985-gene) and histopathological hallmarks of focal outfoldings of myelin in nerve biopsies indicate to the CMT4B1/2-locus (MTMR2- and SBF2-gene). Finally this study demonstrates an increased detection rate of early childhood onset HSMN by the combination of exact phenotypically description, genotyping and mutation analysis.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Makowski, Astrid

Contributors dc:contributor

• Zerres, Klaus

• info:eu-repo/classification/ddc/610
• Charcot-Marie-Syndrom
• Neuromuskuläre Krankheit
• Kinderheilkunde
• Neurogenetik
• Humangenetik
• Medizin
• CMT
• HMSN
• Neuropathie
• Neuropathy
• neuromuscular disorder
• early childhood onset

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112922%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50375