AHNAK2 – Charcot-Marie-Tooth Disease

AHNAK2 has been proposed as a novel autosomal recessive cause of Charcot-Marie-Tooth disease based on a single consanguineous Malaysian family. Genome-wide linkage mapped the locus to 14q32.11-q32.33, and whole-exome sequencing identified two AHNAK2 missense variants c.118A>C (p.Thr40Pro) ([PMID:31011849]) and c.2743C>T (p.His915Tyr) ([PMID:31011849]) that segregate with disease. Segregation in two affected siblings supports recessive inheritance. Functional studies in patient fibroblasts revealed significantly reduced AHNAK2 mRNA and protein levels and disrupted interaction with periaxin, suggesting a loss-of-function mechanism ([PMID:31011849]). No additional unrelated cases or replication studies have been reported to date. Additional evidence is needed to confirm this gene-disease association and establish clinical testing guidelines.

References

• Neurogenetics • 2019 • Linkage analysis and whole exome sequencing reveals AHNAK2 as a novel genetic cause for autosomal recessive CMT in a Malaysian family PMID:31011849

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