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Case Reports
. 2021 May;8(5):1158-1164.
doi: 10.1002/acn3.51364. Epub 2021 May 4.

Charcot-Marie-Tooth disease type 2F associated with biallelic HSPB1 mutations

Elena Abati  1 , Stefania Magri  2 , Megi Meneri  3 , Giulia Manenti  1 , Daniele Velardo  3 , Francesca Balistreri  2 , Chiara Pisciotta  4 , Paola Saveri  4 , Nereo Bresolin  1   3 , Giacomo Pietro Comi  1   3 , Dario Ronchi  1 , Davide Pareyson  4 , Franco Taroni  2 , Stefania Corti  1   3
Affiliations
Case Reports

Charcot-Marie-Tooth disease type 2F associated with biallelic HSPB1 mutations

Elena Abati et al. Ann Clin Transl Neurol. 2021 May.

Abstract

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Domain architecture of HSPB1 and localization of known HSPB1 mutations. α‐crystallin domain is shown in green. Sites of phosphorylation by MAPKAPK‐2 are shown as red rectangles. All currently known mutations are listed. Biallelic HSPB1 mutations are indicated in bold.
Figure 2
Figure 2
Family pedigree of the probands and Sanger electropherograms of the HSPB1 p.S135F and p.R136L mutations.
See this image and copyright information in PMC

References

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Publication types

Supplementary concepts