Freeman-Sheldon syndrome: a disorder of congenital myopathic origin?

Abstract

The gene for Charcot-Marie-Tooth disease type 1a (CMT1a) has been localised to chromosome 17p11.2. Locus D17S122 is recognised by the DNA probe pVAW409R3 which detects an MspI polymorphism with three alleles in the normal population. Subjects with CMT1a show evidence of trisomy for this region of chromosome 17 by displaying either all three alleles or a dosage effect when only two alleles are present. This phenomenon was seen in 10 out of 11 families with type I hereditary motor and sensory neuropathy (HMSN) where affected subjects were heterozygous for the MspI polymorphisms. This mutation is likely to have arisen from a non-reciprocal recombination event between non-sister chromatids of homologous chromosomes at meiosis I. The detection of this partial trisomy offers a rapid method for the diagnosis of CMT1a in families not suitable for linkage analysis.