The overall goal of these studies is the identification of loci underlying Charcot-Marie-Tooth disease (CMT), the Gilles de la Tourette syndrome (GTS), and the Werdnig-Hoffman (WH) form of spinal muscular atrophy. Autosomal dominant CMT is clinically heterogeneous, primarily affecting the Schwann cell (hereditary motor-sensory neuropathy (HMSN) I) or the axon (HMSN II). The locus for HMSN Ib is on chromosome 1; no linkage is known for the clinically identical HMSN Ia or for HMSN II. GDLT is an autosomal dominant disorder with variable expressivity for which no linkage has been established but has been associated in one kindred with a balanced translocation involving chromosome 18. WH is a lethal autosomal recessive trait for which no linkage information exists. Multiple large kindreds, already ascertained, segregating CMT or GDLT, will be tested initially for linkage to chromosome 1 or 18 markers. Nonlinked kindreds, including an HMSN II kindred containing two probable homozygotes, will be further analyzed by multi locus linkage analysis, using markers spanning the human genome. WH occurring in consanguineous matings will be analyzed by homozygosity mapping. Information derived from these studies will be useful for classification of the heterogeneous CMT syndromes, for genetic counselling, and for eventual identification of the genes underlying these disorders.