Mutations in the DNAJB6 gene cause limb girdle muscular dystrophy D1 (LGMD D1) and distal myopathy with rimmed vacuoles. With the discovery of new mutations, the phenotypic spectrum of DNAJB6-related myopathy has been extended, making the diagnosis more complicated. In this study, we describe a female carrier of spinal and bulbar muscular atrophy (SBMA) diagnosed with DNAJB6-related distal myopathy. The c.292_294delGAT (p. Asp98del) mutation in the DNAJB6 gene and a 49 CAG repeat expansion in the androgen receptor (AR) gene were identified. According to the clinical manifestations of distal-dominant lower limb involvement, a myogenic pattern in the electrophysiological study, and rimmed vacuoles on muscle pathology, the patient was ultimately diagnosed with DNAJB6-related distal myopathy. A functional study in a zebrafish model indicated that the c.292_294delGAT (p. Asp98del) mutation contributed to muscle structure defects. This study offers useful insights for the differential diagnosis of a condition in which patients carry pathogenic variants in different genes.
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The authors would like to express sincere gratitude to the patient and family for their cooperation in this study. Furthermore, this work was supported by Youth Innovation Fund in Neurology.
The authors declare no competing interests.
Ethics approval and consent to participate
This study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of the Cheeloo College of Medicine, Shandong University. The patient and her family members provided written informed consent for genetic analysis, muscle biopsy, and publication of this report.
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Xu, L., Geng, H., Lv, X. et al. A female carrier of spinal and bulbar muscular atrophy diagnosed with DNAJB6-related distal myopathy. J Hum Genet 67, 441–444 (2022). https://doi.org/10.1038/s10038-022-01022-3