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

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.

Clinical, Electrophysiological and Molecular Features in Hereditary Neuropathy with Liability to Pressure Palsies

Introduction: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant inherited peripheral neuropathy caused by deletions of the PMP22 gene (PMP22). It is classically characterized by episodes of repeated focal pressure neuropathies at common entrapment sites. Atypical forms are recognized and may occur in up to 56% of HNPP patients. The electrophysiological characteristics and the genetic studies are paramount for its diagnosis. We aim to describe clinical, electrophysiological and genetic features of a cohort of patients diagnosed with HNPP at a tertiary hospital. Methods: Retrospective study of patients with a confirmed diagnosis of HNPP, using descriptive statistics for their characterization. Results: Seventeen patients from 15 different families were included. Nine were males, and the overall mean age was 42.6 years-old. Age at first symptoms ranged from 3 to 46 years-old, with mean time until diagnosis of 9.3 years. Nine patients (53%) presented recurrent painless mononeuropathies or isolated focal compressive neuropathies, and eight patients (47%) had atypical presentation phenotypes, such as “Charcot-Marie-Tooth-like (CMT-like) and sensory neuropathy. Intra-familial clinical heterogeneity was observed. All patients showed nerve conduction slowing at common entrapment sites (median, ulnar and peroneal nerves), and signs of a more generalized peripheral nerve involvement were present in more than half of the patients. Fifteen patients carried the PMP22 gene deletion, and point mutations were present in two. Conclusion: Our cohort presents similar clinical characteristics to the literature description, with a significant proportion of patients with atypical presentations. The absence of clinical-electrophysiological correlation emphasise the importance of nerve conduction and genetic studies for the definite diagnosis of the disease.

Investigation on the deletion and duplication of PMP22 gene in patients with Charcot-Marie-Tooth using Real-time PCR in Chaharmahal and Bakhtiari and Isfahan Provinces

Background and aims: Charcot-Marie-Tooth (CMT) is a common sensory-motor polyneuropathy with a prevalence of 1/2500. It is divided into different subgroups and has various hereditary patterns. Among the different subgroups of CMT, type 1A is the most prevalent form of the disease, which is created due to the duplication of the PMP22 gene. In patients has a deletion in the PMP22 gene, the hereditary neuropathic disease is known to be liable to pressure. The aim of this study was to identify the patients affected by the disease with the new, simple, and fast qPCR method and to investigate the appropriateness of this method in evaluating these types of mutations. Methods: In this analytical-descriptive study (code:IR.SKUMS.REC.1394.152), gene duplication and deletion in the patients were studied using the Excel software. The blood samples of 15 families afflicted with CMT and 49 healthy individuals were collected in EDTA anticoagulant tubes and analyzed. DNA extraction and quantitative real-time PCR method were applied for the PMP22 gene as the target gene and the albumin gene as the internal control gene. Results: Two genes were compared in each patient, and it was found that 46% of the subjects had duplication in the PMP22 gene. Conclusion: The qPCR method is an easy and fast way to detect gene duplication and deletion in CMT patients. It does not require any statistical software and can be performed without needing for parental DNA. In addition, the results of this study are consistent with the results of various studies in some countries of the world where the highest levels of deletion and duplication in PMP22 gene are seen.