Update on an Asian Indian Family With Apparent Autosomal Recessive Charcot-Marie-Tooth Disease Caused by a Mutation in the HSPB1 Gene

Background: We described an Asian Indian family with a genetic neuropathy previously in the Journal of Neurology Research, 2012. In that publication, we speculated that a deletion mutation in the PRX gene may have contributed to the development of the neuropathy. In this family, there is significant phenotypic variability which created difficulties establishing the mode of transmission which appeared to be autosomal recessive. We now present our updated analysis with additional clinical and genetic data. Methods: We obtained clinical and phenotype data on additional members of this family. We performed whole exome sequencing on the index patient and targeted genotyping of other members of the family. Results: Our updated analysis establishes the pattern of inheritance of this neuropathy as autosomal dominant and caused by a mutation in the HSPB1 gene, R140G. The R140G mutation has been previously reported in a number of unrelated families originating from Gujarat, the same Indian state as the subjects of this study. Conclusions: The collective genetic analysis of this mutation in the Gujarati families suggests the presence of a founder effect of the R140G mutation in this population. Our investigation of this family demonstrates the capacity of next generation sequencing in facilitating the ability to make a specific genetic diagnosis. J Neurol Res. 2019;9(4-5):60-64 doi: https://doi.org/10.14740/jnr547