HOMOZYGOSITY MAPPING OF A NEW LOCUS FOR AN AUTOSOMAL RECESSIVE FORM OF DISTAL HEREDITARY MOTOR NEUROPATHY (dHMN)

Distal Hereditary Motor Neuropathy (dHMN) are characterized by a motor but not sensory involvement of the peripheral nervous system. Clinically, 7 variants have been described, even though only 5 loci found: 3 for autosomal dominant forms (dHMN II, V and VII) and 2 for recessive forms (dHMN J and VI). A large family, living in a small and geographically isolated village of South Italy, with some subjects with a dHMN diagnosis, has clinically been observed. Since four consanguinity marriages have been found, an autosomal recessive inheritance has been postulated. Due to similar pathological phenotypes, the genes for CMT1 (PMP22 and P0) and for SMA (SMN) have been excluded by a mutational screening. Moreover, a linkage exclusion has been carried out for the recessive dHMNs till now identified (III and VI), obtaining significantly negative LOD score values (<-2). On this basis, we may assume that this is a new clinical and genetic entity. For this reason we propose to map the disease gene by means of a genome wide search. For this study, 482 microsatellites will be used, covering the entire genome, in order to find the homozygous region present only in the affected subjects; in this interval the candidate gene will be analysed. The identification of a new disease gene is the starting point in the understanding of the pathogenesis of dHMN and in the correlated forms of motor neuropathies. This is of great importance since no efficient treatment is still available.