A Locus for Axonal Motor-sensory Neuropathy with Deafness and Mental Retardation Maps to Xq24-q26

DNA markers on the X chromosome were used to map the locus for an unusual form of X-linked recessive hereditary motor and sensory neuropathy with associated deafness and mental retardation in a three-generation family that was originally reported by Cowchock et al. (Am, J. Hum. Genet. 35: 85A, 1993; Am. J. Med. Genet. 20: 307-315, 1985). This family included seven affected males, three obligate carrier females, and four unaffected males. The patients were severely affected within the first few years of life with distal weakness, muscle atrophy, sensory loss, areflexia, pes cavus, and hammer toes. Five of the seven affected males showed associated deafness, and three of these five individuals also presented with mental retardation or social developmental delay. Motor nerve conduction velocities in affected males were normal to mildly delayed, and sensory conduction was markedly abnormal. Heterozygous females were asymptomatic. Close linkage to the Xg blood group locus (Xp22) and the PGK locus (Xq13) was previously excluded in this family, while weak linkage of the disease gene to DXYS1 (XQ21.3) was suggested. Our current linkage studies and haplotype analysis of 19 microsatellite markers on the long arm of the X chromosome demonstrate that DXS425 (Xq24) and HPRT (Xq26.1) are flanking markers and that the disease gene is closely linked to the markers DXS1122, DXS994, DXS737, DXS1206, and DXS1047.