Open AccessCharcot–Marie–Tooth disease type 2F associated with biallelic HSPB1 mutations
Author(s) -
Abati Elena,
Magri Stefania,
Meneri Megi,
Manenti Giulia,
Velardo Daniele,
Balistreri Francesca,
Pisciotta Chiara,
Saveri Paola,
Bresolin Nereo,
Comi Giacomo Pietro,
Ronchi Dario,
Pareyson Davide,
Taroni Franco,
Corti Stefania
Publication year - 2021
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51364
Subject(s) - medicine , mutation , genetics , in silico , genetic testing , gene , disease , bioinformatics , pathology , biology
Objective This work aims to expand knowledge regarding the genetic spectrum of HSPB1 ‐related diseases. HSPB1 is a gene encoding heat shock protein 27, and mutations in HSPB1 have been identified as the cause of axonal Charcot–Marie–Tooth (CMT) disease type 2F and distal hereditary motor neuropathy (dHMN). Methods Two patients with axonal sensorimotor neuropathy underwent detailed clinical examinations, neurophysiological studies, and next‐generation sequencing with subsequent bioinformatic prioritization of genetic variants and in silico analysis of the likely causal mutation. Results The HSPB1 p.S135F and p.R136L mutations were identified in homozygosis in the two affected individuals. Both mutations affect the highly conserved alpha‐crystallin domain and have been previously described as the cause of severe CMT2F/dHMN, showing a strictly dominant inheritance pattern. Interpretation Thus, we report for the first time two cases of biallelic HSPB1 p.S135F and p.R136L mutations in two families.