Identifizierung und Charakterisierung des Gens für die autosomal rezessiv erbliche Charcot-Marie-Tooth-Neuropathie Typ 4C (CMT4C)

Hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth neuropathy (CMT) is the most common inherited neuromuscular disorder. In most of the families, HMSN is inherited as an autosomal dominant or X-linked trait. In Western Europe, autosomal recessive HMSN (AR-HMSN) is much less common than the dominant forms. However, in communities with a high prevalence of consanguineous marriages, autosomal recessive HMSN accounts for up to 50% of all HMSN cases. AR-HMSN is clinically and genetically heterogeneous. In this study an AR-HMSN locus on chromosome 5q (CMT4C) was refined to 1.7 Mb using homozygosity mapping and haplotype sharing analysis in two consanguineous Turkish families. Eight known genes and eight anonymous transcripts mapped within the 1,7 Mb CMT4C region. Mutation analysis of candidate genes was performed in families with putative CMT4C. Pathogenic mutations were detected in 12 families in the KIAA1985 gene, a so far uncharacterised transcript. KIAA1985 encodes a new protein of unknown function and belongs to a novel protein family conserved during vertebrate evolution. KIAA1985 is expressed in the peripheral nervous system and seems to localize to the plasma membrane. According to its predicted domain structure the KIAA1985 protein may act as an adapter or docking molecule mediating protein protein interactions. Mutations in KIAA1985 are a relatively frequent cause of AR-HMSN and may also account for sporadic HMSN cases. The results of this study will aid genetic testing and counseling in families with recessive and sporadic HMSNs. Functional studies and protein protein interaction assays on the CMT4C protein will add to our knowledge of pathomechanisms in neuromuscular disorders. As KIAA1985 is a novel protein of unknown function, its characterization may shed light on so far unknown molecular and cellular mechanisms of disease.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Stendel, Claudia

Contributors dc:contributor

• Zerres, Klaus

• info:eu-repo/classification/ddc/610
• Medizin
• Charcot-Marie-Tooth-Neuropathie
• Hereditäre Motorische und Sensorische Neuropathie
• Mutation
• KIAA1985

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114418%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A52180