32 Schreiber, Susanne Margarete Zerres, Klaus 525000-2 Publikationsserver der RWTH Aachen University Aachen German 45 S. : Ill., graph. Darst. The hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth neuropathies are the most common hereditary neuromuscular disorder. In most families the disorder follows an autosomal dominant or X-linked mode of inheritance. Autosomal recessive HMSN (AR-HMSN) is rare in Western Europe, however, in geographic regions and populations with a high incidence of consanguineous marriages it is responsible for up to 50% of all HMSN cases. AR-HMSN is genetically heterogeneous. In a subset of patients with AR-HMSN nerve biopsies show characteristic myelin outfoldings (focally folded myelin). In this study I performed a targeted search for mutations in the genes SBF2, MTMR2 and KIAA1985 in AR-HMSN families with focally folded myelin in the nerve biopsies. Disease-causing mutations were detected in seven out of 17 cases: four families showed mutations in the SBF2 gene, one family in the MTMR2 gene and two families in the KIAA1985 gene. The progression and the severity of the neuropathy seemed to be related to the affected gene: the mutation in the MTMR2 gene resulted in a severe neuropathy with an early onset and fast progression of symptoms while SBF2 mutations were associated with a milder phenotype. The course of the disease was highly variable in patients with KIAA1985 mutations, however, early onset scoliosis was a constant trait in these cases. Mutation analysis of the SBF2, MTMR2 and KIAA1985 genes is effective in cases with a characteristic phenotype. However, in more than half of the patients no mutation could be found in the investigated genes suggesting the existence of other genes that cause AR-HMSN with focally folded myelin. The identification of these genes will provide new insights into the pathophysiology of the peripheral nervous system. Aachen, Techn. Hochsch., Diss., 2009 ; PUB:(DE-HGF)11, ; 2, ; Charcot-Marie-Syndrom Molekulargenetik Dissertation / PhD Thesis 2009 RWTH-CONV-113923 2009 https://publications.rwth-aachen.de/record/51653