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. 2013 Jun;47(6):922-4.
doi: 10.1002/mus.23743. Epub 2013 Mar 29.

Re-analysis of an original CMTX3 family using exome sequencing identifies a known BSCL2 mutation

Rabia Chaudhry  1 , Aditi Kidambi, Megan Hwa Brewer, Anthony Antonellis, Katherine Mathews, Garth Nicholson, Marina Kennerson
Affiliations

Re-analysis of an original CMTX3 family using exome sequencing identifies a known BSCL2 mutation

Rabia Chaudhry et al. Muscle Nerve. 2013 Jun.

Abstract

Introduction: Charcot-Marie-Tooth (CMT) disease is a group of peripheral neuropathies affecting both motor and sensory nerves. CMTX3 is an X-linked CMT locus, which maps to chromosome Xq26.3-q27.3. Initially, CMTX3 was mapped to a 31.2-Mb region in 2 American families. We have reexamined 1 of the original families (US-PED2) by next generation sequencing.

Methods: Three members of the family underwent exome sequencing. Candidate variants were validated by PCR and Sanger sequencing analysis.

Conclusion: No pathogenic coding variants localizing to the CMTX3 region were identified. However, exome sequencing identified a known BSCL2 mutation (N88S). This study demonstrates the power of exome sequencing as a tool to identify gene mutations for a small family in the absence of statistically significant linkage data.

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Figures

FIGURE 1
FIGURE 1
Identification and validation of a known BSCL2 gene mutation in US-PED2. (a) Filtering strategy to identify shared variants in the affected man and obligate carrier woman. This method enabled the identification of potential pathogenic mutations in the CMTX3 region as well as in known peripheral neuropathy genes. (b) Mapped exome sequence reads in the Integrative Genomics Viewer (IGV)23 for the affected man from US-PED2. The gray bar represents the reference allele (T), and the colored base indicates the alternative allele (C). (c) Sequence traces showing the validation of the change identified by Sanger sequencing. Both the affected and obligate carrier individuals were heterozygous for the change c.263A>G (NM_032667). *Other regions represent the X chromosome, apart from the CMTX3 region, and the autosomes.
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