DNA rearrangements on both homologues of chromosome 17 in a mildly delayedindividual with a family history of autosomal dominant carpal tunnel syndrome

Disorders known to be caused by molecular and cytogenetic abnormalities of the proximal short arm of chromosome 17 include Charcot-Marie-Tooth disease type 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), Smith-Magenis syndrome (SMS), and mental retardation and congenital anomalies associated with partial duplication of 17p. We identified a pati ent with multifocal mononeuropathies and mild distal neuropathy, growth hor mone deficiency, and mild mental retardation who was found to have a duplic ation of the SMS region of 17p11.2 and a deletion of the peripheral myelin protein 22 (PMP22) gene within 17p12 on the homologous chromosome. Further molecular analyses reveal that the dup(17)(p11.2p11.2) is a de novo event b ut that the PMP22 deletion is familial. The family members with deletions o f PMP22 have abnormalities indicative of carpal tunnel syndrome, documented by electrophysiological studies prior to molecular analysis. The chromosom al duplication was shown by interphase FISH analysis to be a tandem duplica tion. These data indicate that familial entrapment neuropathies, such as ca rpal tunnel syndrome and focal ulnar neuropathy syndrome, can occur because of deletions of the PMP22 gene. The co-occurrence of the 17p11.2 duplicati on and the PMP22 deletion in this patient likely reflects the relatively hi gh frequency at which these abnormalities arise and the underlying molecula r characteristics of the genome in this region.