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Ser135Phe mutation in HSPB1 (HSP27) from Charcot–Marie–Tooth disease type 2F families

Kim, Hye Jin, Lee, Jinho, Hong, Young Bin, Kim, Ye Jin, Lee, Ja Hyun, Nam, Soo Hyun, Choi, Byung-Ok, Chung, Ki Wha
Genes & genomics 2015 v.37 no.3 pp. 295-303
genes, heat shock proteins, mutation, peripheral nervous system diseases, phenotype, sequence analysis
Charcot–Marie–Tooth disease (CMT) is a group of clinically and genetically heterogeneous peripheral neuropathies. We identified two axonal CMT type 2F (CMT2F) families presented with distally predominant weakness in upper and lower extremities with sensory involvement. This study identified a c.404C>T (p.Ser135Phe) mutation in HSPB1 gene as the underlying cause of the both families by applying of whole exome sequencing. The p.Ser135Phe mutation was completely cosegregated with the affected members in the both families, and it was not found in 300 healthy controls. This mutation has been previously reported as the causes of CMT2F or hereditary motor neuropathy 2B (dHMN2B). The mutation was located in the highly conserved alpha-crystallin domain, and several in silico analyses also predicted that the mutation is likely to be pathogenic. HSPB1 encodes heat shock protein 27 (HSP27) which belongs to the superfamily of small stress induced proteins. These results suggest that the HSPB1 mutation is underlying cause of CMT2F phenotype shown in the present families. We believe that this study will be useful for the molecular diagnosis of peripheral neuropathies.