Mutation analysis of PMP22 in Slovak patients with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies

Abstract

Abstract. Charcot-Marie-Tooth disease (CMT) and related peripheral neuropathies are the most commonly inherited neurological disorders in humans, characterized by clinical and genetic heterogeneity. The most prevalent clinical entities belonging to this group of disorders are CMT type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A and HNPP are predominantly caused by a 1.5 Mb duplication and deletion in the chromosomal region 17p11.2, respectively, and less frequently by other mutations in the peripheral myelin protein 22 (PMP22) gene. Despite being relatively common diseases, they haven't been previously studied in the Slovak population. Therefore, the aim of this study was to identify the spectrum and frequency of PMP22 mutations in the Slovak population by screening 119 families with CMT and 2 families with HNPP for causative mutations in this gene.The copy number determination of PMP22 resulted in the detection of CMT1A duplication in 40 families and the detection of HNPP deletion in 7 families, 6 of which were originally diagnosed as CMT. Consequent mutation screening of families without duplication or deletion using dHPLC and sequencing identified 6 single base changes (3 unpublished to date), from which only c.327C>A (Cys109X) present in one family was provably causative.These results confirm the leading role of PMP22 mutation analysis in the differential diagnosis of CMT and show that the spectrum and frequency of PMP22 mutations in the Slovak population is comparable to that seen in the global population.

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

“…In Ukrainian patients, several cases of duplication in this region without a family history of disease were found, with the greatest cause reported to be duplication in the PMP22 gene, which accounted for 95% of the cases (18). In another study, 119 families from Slovakia with CMT were examined, out of whom 40 had gene duplication and 7 had gene deletion (19). In a large study in the United States of America, 95% of the positive results belonged to four genes: PMP22, MPZ, MFN2, and GJB1.…”

Anesthetic Considerations for Patients with Hereditary Neuropathy with Liability to Pressure Palsies: A Narrative Review

“…The current reported prevalence of HNPP is in the range of 7-16:100,000; however, this may be a conservative estimate due to underdiagnosis [2,7,10,15,17,[37][38][39][40][41][42][43]. Misdiagnosis or underdiagnosis may be partly attributed to the subtle clinical features and variable presentation of the disease [4,27,35,[44][45][46][47][48].…”

Molecular genetic diagnosis and clinical features of hereditary neuropathy with liability to pressure palsies

“…снижение дозы гена РМР22) лежит в основе развития ННППС. Таким образом, результатом разнонаправленных нарушений дозы гена РМР22 (делеция или дупликация) являются два различных неврологических заболевания, при этом, благодаря общей генетической природе, существуют единые подходы к их диагностике [5,6].…”