Charcot‐marie‐tooth neuropathy related to chromosome 1

Abstract

One family with documented male‐to‐male transmission of Charcot‐Marie‐Tooth (CMT) neuropathy was studied clinically and by genetic linkage. Patients had progressive distal weakness and atrophy, areflexia, and distal sensory loss, but early onset (before age 3 years) in all 5 cases, and phrenic nerve involvement in the propositus (a 39‐year‐old woman) requiring CPAP ventilator support during the night. Motor‐nerve conduction velocities (MNCVs) were significantly slow, consistent with severe demyelinating neuropathy. Electromyography (EMG) data were normal. Two‐point and multipoint linkage analyses strongly suggested the presence of a CMT gene on chromosome 1q. A maximum multipoint lod score of 2.70 was obtained at MUCI (θ = 0), with the locus order centromere‐MUC1‐SPTA1‐FcγRII‐AT3‐telomere. Multipoint linkage analysis excluded the CMT locus from chromosome 17 markers in this family.