Abstract
Hereditary neuropathy with liability to pressure palsies (HNPP) has been a associated with a deletion of 1.5 megabases of chromosome 17p. One of four biopsy proven HNPP families that we have studied did not possess this deletion. As the deleted DNA region includes the coding region for a peripheral myelin gene (PMP22), we used single strand conformation analysis to examine this gene for mutations in the non–deleted HNPP family. An abnormal fragment in exon 1 was identified, and sequencing revealed a two base pair deletion in all affected family members. The deletion results in a frame shift, providing strong evidence that this gene has an important role in the pathogenesis of the disease.
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References
Davies, D.M. Recurrent peripheral-nerve palsies in a family. Lancet 2, 266–268 (1954).
Earl, C.J., Fullerton, P.M., Wakefield, G.S. & Schutta, H.S. Hereditary neuropathy with liability to pressure palsies. Quart. J. Med. 33, 481–498 (1964).
Meier, C. & Moll, C. Hereditary neuropathy with liability to pressure palsies. J. Neurol. 228, 73–95 (1982).
Taylor, R.A. Heredofamilial mononeuritis multiplex with brachial predilection. Brain 83, 113–137 (1960).
Bradley, W.G., Madrid, R., Thrush, D.C., Campbell, M.J. Recurrent brachial plexus neuropathy. Brain 98, 381–398 (1975).
Barbieri, F. et al. A family with tomaculous neuropathy mimicking Chareot-Marie-Tooth disease. Clin. Neurol. Neurosurg. 92–3, 289–294 (1990).
Madrid, R. & Bradley, W.G. The pathology of neuropathies with focal thickening of the myelin sheath (Tomaculous Neuropathy). J. neurol. Sci. 25, 415–448 (1975).
Chance, P.F. et al. DNA Deletion Associated with Hereditary Neuropathy with Liability to Pressure Palsies. Cell 72, 143–151 (1993).
Pentao, L., Wise, C.A., Chinault, A.C., Patel, P.I. & Lupski, J.R. Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet. 2, 292–300 (1992).
Lupski, J.R. et al. Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 29–33 (1992).
Chance, P.F. et al. Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: Evidence for gene dosage as a mechanism in CMT1A. Neurology 42, 2295–2299 (1992).
Valentijn, L.J. et al. The peripheral myelin gene /GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 166–170 (1992).
Valentijn, L.J. et al. Identical point mutations of in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A. Nature Genet. 2, 288–291 (1992).
Roa, B.B. et al. Charcot-Marie-Tooth disease type 1A associated with a de novo point mutation in the PMP22 gene. New Engl. J. Med. 329, 96–101 (1993).
Kulkens, T. et al. Deletion of the serine 34 codon from the major peripheral myelin Po gene in Charcot-Marie-Tooth disease type 1B. Nature Genet. 5, 35–39 (1993).
Hayasaka, K. et al. Isolation and sequence determination of cDNA encoding (PAS-II/SR13/Gas-3) of human peripheral myelin. Biochem. Biophys. Res. Commun. 186, 827–831 (1992).
McIntosh, I., Hamosh, A. & Dietz, H.C. Nonsense mutations and diminished mRNA levels. Nature Genet. 4, 219 (1993).
Davies, K. Peripherin and the vision thing. Nature 362, 92 (1993).
Travis, G.H. & Hepler, J.E. A medley of retinal dystrophies. Nature Genet. 3, 191 (1993).
Bascom, R.A. et al. Rom 1: a candidate gene for autosomal dominant retinitis pigmentosa (ADRP), Usher syndrome type 1, and Best vitelliform macular dystrophy. Am. J. hum. Genet. 51, suppl, A6 (1992).
Hayasaka, K. et al. Charcot-Marie-Tooth type 1B is associated with mutations of the myelin Po gene. Nature Genet. 5, 31–34 (1993).
Hayasaka, H. et al. De-novo mutation of the myelin Po gene in hereditary motor and sensory neuropathy type HI (Dejerine-Sottas disease). Nature Genet. 5, 266–268 (1993).
Nicholson, G.A. Penetrance of the hereditary motor and sensory neuropathy 1A-mutation — assessment by nerve conduction studies. Neurology 41, 547–552 (1991).
Patel, P.I. et al. The gene for the peripheral myelin protein is a candidate for Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 159–165 (1992).
Nicholson, G.A. et al. The Charcot-Marie-Tooth neuropathy type 1a mutation: Apparent crossovers with D17S122 are due to a duplication. Am. J. med. Genet. 44, 455–460 (1992).
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Nicholson, G., Valentijn, L., Cherryson, A. et al. A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies. Nat Genet 6, 263–266 (1994). https://doi.org/10.1038/ng0394-263
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DOI: https://doi.org/10.1038/ng0394-263
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