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DOI: 10.1055/s-0039-3400985
A Case of Severe Early-Onset Neuropathy Caused by a Compound Heterozygous Deletion of the PMP22 Gene: Clinical and Neurographic Aspects
Publication History
22 July 2019
06 October 2019
Publication Date:
29 November 2019 (online)
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Abstract
Heterozygous deletions of the gene PMP22 are associated to hereditary neuropathy with liability to pressure palsies (HNPP), a demyelinating neuromuscular disease causing variable transitory focal muscles weakness. Deletions involving both copies of PMP22 cause more severe phenotypes, with early-onset neuropathy and impairment in motor development. We report a patient with a severe early-onset demyelinating neuropathy, caused by two different inherited deletions of PMP22, whose parents had an HNPP. The patient showed neurological signs and delay in motor development but normal intellective abilities. A motor and sensitive conduction study showed severe signs of demyelination, suggestive for Dejerine Sottas Syndrome (DSS). The patient's father had a typical HNPP caused by a heterozygous 17p11.2 deletion, encompassing PMP22. The patient's mother reported no neuropathic symptoms, but in a nerve conduction studies, parents and several relatives showed signs of sensory–motor deficit with focal slowing of conduction at common sites of entrapment. Quantitative analysis of PMP22, performed in our patient by multiplex ligation-dependent probe amplification, revealed a compound heterozygous status with the same deletion of the father and a deletion of PMP22 exon 5, after proved to be inherited from the mother. Therefore, when we face an early-onset, severe form of neuropathy, we have to consider rare forms of hereditary neuropathy caused by homozygous or compound heterozygous mutations in PMP22, even if parents are asymptomatic; an exhaustive family history and an electrodiagnostic study are essential to guide genetic tests and to make a diagnosis.
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References
- 1 Baets J, Deconinck T, De Vriendt E. , et al. Genetic spectrum of hereditary neuropathies with onset in the first year of life. Brain 2011; 134 (Pt 9): 2664-2676
- 2 Mathis S, Goizet C, Tazir M. , et al. Charcot-Marie-Tooth diseases: an update and some new proposals for the classification. J Med Genet 2015; 52 (10) 681-690
- 3 Snipes GJ, Suter U, Welcher AA, Shooter EM. Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13). J Cell Biol 1992; 117 (01) 225-238
- 4 Li J, Parker B, Martyn C, Natarajan C, Guo J. The PMP22 gene and its related diseases. Mol Neurobiol 2013; 47 (02) 673-698
- 5 Rudnik-Schöneborn S, Auer-Grumbach M, Senderek J. Hereditary neuropathies: update 2017. Neuropediatrics 2017; 48 (04) 282-293
- 6 Beydoun SR, Cho J. Hereditary neuropathy with liability to pressure palsy: two cases of difficult diagnosis. J Clin Neuromuscul Dis 2013; 15 (01) 28-33
- 7 Al-Thihli K, Rudkin T, Carson N, Poulin C, Melançon S, Der Kaloustian VM. Compound heterozygous deletions of PMP22 causing severe Charcot-Marie-Tooth disease of the Dejerine-Sottas disease phenotype. Am J Med Genet A 2008; 146A (18) 2412-2416
- 8 Abe A, Nakamura K, Kato M. , et al. Compound heterozygous PMP22 deletion mutations causing severe Charcot-Marie-Tooth disease type 1. J Hum Genet 2010; 55 (11) 771-773
- 9 Saporta MA, Katona I, Zhang X. , et al. Neuropathy in a human without the PMP22 gene. Arch Neurol 2011; 68 (06) 814-821
- 10 Takahashi S, Chum M, Kimpinski K. Electrodiagnostic characterization of hereditary neuropathy with liability to pressure palsies. J Clin Neuromuscul Dis 2017; 18 (03) 119-124