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November 17, 1993

Inherited Primary Peripheral NeuropathiesMolecular Genetics and Clinical Implications of CMT1A and HNPP

Author Affiliations

From the Institute for Molecular Genetics, the Department of Pediatrics, and the Human Genome Center, Baylor College of Medicine, and the Texas Children's Hospital, Houston (Dr Lupski); the Division of Medical Genetics, Department of Pediatrics, University of Utah Medical Center, Salt Lake City (Dr Chance); and the Departments of Neurology and Pathology, Louisiana State University School of Medicine, New Orleans (Dr Garcia). Dr Chance is now at the Division of Neurology, Children's Hospital of Philadelphia, Pa.

JAMA. 1993;270(19):2326-2330. doi:10.1001/jama.1993.03510190082031

CHARCOT-MARIE-TOOTH disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant, inherited primary demyelinating peripheral neuropathies that appear to result from reciprocal DNA duplication/deletion, respectively, of a 1.5-megabase (Mb) pair region on chromosome 17p. While inherited DNA rearrangements are present in most CMT1A and HNPP patients, new mutation duplication or deletion can be responsible for sporadic cases of CMT1A or HNPP. This critical 1.5-Mb region is likely to contain multiple genes, but a dosage effect of one gene that encodes a myelin protein of the peripheral nerve (PMP22) appears to play a critical role in the disease phenotype. Moreover, PMP22 point mutations associated with CMT1A have been identified in patients who do not have the CMT1A duplication. The recent elucidation of the molecular mechanisms for CMT1A and HNPP has important clinical implications for the diagnosis, prognosis, genetic counseling, and rational approaches to therapy for