A New Point Mutation in the PMP22 Gene in a Family Suffering From Atypical HNPP

Abstract

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder commonly presenting with acute-onset, non-painful focal sensory and motor mono neuropathy. In 80% of cases, the genetic defect is a 1.5 Mb deletion on chromosome 17p11.2, including PMP22. Only few cases of partial deletion and point mutations in PMP22 are involved in HNPP. We investigated a 62-years-old man with lower limb plexopathy first considered as Garland’s syndrome. A month later, his 29 years old son also consulted for paresthesia on the peroneal nerve. Targeted sequencing of the PMP22 gene identified a c.370delT (p.Trp124Glyfs*31) in both affected patients. We report a new PMP22 point mutation associated with an atypical clinical phenotype of HNPP, a painful plexopathy of the lower limb worsenen by diabetes and a mere paresthesia, but a typical ENMG. This study illustrates the large spectrum of the disease, and emphasizes the importance of a complete ENMG and family history.

Noncanonical splice‐site variant in peripheral myelin protein 22 gene (PMP22) in a patient with hereditary neuropathy with liability to pressure palsies

“…PMP22 is expressed in peripheral nerves and the protein product is a constituent of myelin. Several splice‐site variants in PMP22 in HNPP have been reported to date 13 . The loss of PMP22 increases the permeability of myelin to potassium ions leading to elevated resting potentials, which disturb the propagation of action potentials.…”

“…in HNPP have been reported to date. 13 The loss of PMP22 increases the permeability of myelin to potassium ions leading to elevated resting potentials, which disturb the propagation of action potentials. Among reported variants located at the canonical splice site or in its vicinity causing HNPP, two variants, namely, c.78 + 1G > T 3 and c.78 + 5G > A 4 were located in the same canonical splice donor site or its downstream region at the exon 2-intron 2 junction in PMP22.…”

Tibial neuropathy, a rare manifestation of hereditary neuropathy with liability to pressure palsy: A case report

“…Moreover, the heterozygosity loss of her mother, and the 1.43mbDNA deletion of chromosome 17p12 of her maternal uncle and male cousin, undoubtedly provided evidence for our diagnosis. Except for deletions, previous reports suggest that a small number of PMP22 gene mutations in HNPP are point mutations [ [20] , [21] , [22] ], and there are more than 20 small mutations have been found so far.…”