BAG3 p.Pro209Ser mutation identified in a Chinese family with Charcot-Marie-Tooth disease

Abstract

Bcl2-associated athanogene 3 (BAG3) gene mutations cause dilated cardiomyopathy and myofibrillar myopathy. Recently, a novel c.625C>T (p.Pro209Ser) mutation in BAG3 was reported to cause axonal Charcot-Marie-Tooth (CMT) disease in three families. Here, we describe two patients with adult-onset and moderate CMT in a Chinese family. Nerve conduction velocity studies revealed an axonal sensorimotor neuropathy, which was supported by sural nerve biopsy. Lower limb magnetic resonance imaging (MRI) revealed fatty infiltration more severe in the soleus and deep posterior compartment muscles than in the medial gastrocnemius and anterior compartment muscles. Whole exome sequencing identified the same c.625C>T (p.Pro209Ser) mutation in BAG3, which co-segregated with the CMT disease in this family. This study further enforces the association between BAG3 gene and CMT disease, indicating that BAG3 should be considered in the genetic testing for CMT. The p.Pro209Ser mutation with different ethnic origins might be another hotspot mutation of BAG3. MRI is helpful to detect accurate extent of muscle involvement.

Keywords: Axonal; BAG3; Charcot–Marie–Tooth disease; Hotspot mutation; MRI; Nerve biopsy.