DNA Rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome

Lorraine Potocki, Ken Shiung Chen, Thearith Koeuth, James Killian, Susan T. Iannaccone, Stuart K. Shapira, Catherine D. Kashork, Aimee S. Spikes, Lisa G. Shaffer, James R. Lupski

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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 patient with multifocal mononeuropathies and mild distal neuropathy, growth hormone deficiency, and mild mental retardation who was found to have a duplication 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 but that the PMP22 deletion is familial. The family members with deletions of PMP22 have abnormalities indicative of carpal tunnel syndrome, documented by electrophysiological studies prior to molecular analysis. The chromosomal duplication was shown by interphase FISH analysis to be a tandem duplication. These data indicate that familial entrapment neuropathies, such as carpal tunnel syndrome and focal ulnar neuropathy syndrome, can occur because of deletions of the PMP22 gene. The co-occurrence of the 17p11.2 duplication and the PMP22 deletion in this patient likely reflects the relatively high frequency at which these abnormalities arise and the underlying molecular characteristics of the genome in this region.

Original languageEnglish (US)
Pages (from-to)471-478
Number of pages8
JournalAmerican Journal of Human Genetics
Volume64
Issue number2
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Potocki, L., Chen, K. S., Koeuth, T., Killian, J., Iannaccone, S. T., Shapira, S. K., Kashork, C. D., Spikes, A. S., Shaffer, L. G., & Lupski, J. R. (1999). DNA Rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome. American Journal of Human Genetics, 64(2), 471-478. https://doi.org/10.1086/302240