Clinical analysis of a family with distal-onset DnaJ (heat-shock protein 40) homolog subfamily B member 6 myopathy / 中华神经科杂志

ABSTRACT

Objective:To analyze the clinical manifestations, skeletal muscle pathology, electromyography, skeletal muscle magnetic resonance imaging and gene mutations of a family with distant-onset DnaJ (heat-shock protein 40) homolog subfamily B member 6 (DNAJB6) myopathy.Methods:A total of three generations with three cases of the disease in a family, inherited by autosomal dominant inheritance, were collected. The examination of muscle enzymes, left biceps biopsy, skeletal muscle magnetic resonance imaging (MRI) and electromyography, etc,were performed for the family 's proband. Whole-exon sequencing was performed to screen the proband for pathogenic genes, and Sanger sequencing technology was performed to verify mutation sites of the proband′s family members. Results:The proband is a 30-year-old male who began to show weakness in the distal muscles as a teenager, and then gradually developed to the proximal muscles, accompanied by muscle atrophy of the limbs, mainly affecting small muscles in the hands and distal muscles of the lower limbs. Muscle enzymes of the proband were slightly elevated. Skeletal muscle MRI indicated muscle atrophy and fatty degeneration in the proximal and distal extremities, which in the distal extremities were more severe, mainly affecting the muscle groups of the posterior group. Electromyography indicated chronic myopathic damage. Muscle pathology suggested chronic muscle fiber damage and rimmed vacuoles could be found. The proband was found a heterozygous mutation [c.298T>G(p.F100V)] in DNAJB6 gene by all-exon sequencing. Sanger sequencing confirmed that his brother (similar medical history) and the second daughter also had the same mutation, and the eldest daughter was not detected the mutation at the above site. The second daughter is not ill and is a carrier of the mutation. The father of the proband died of pancreatic cancer and had similar symptoms during his lifetime.Conclusions:The above mutation of DNAJB6 gene is the pathogenic gene of this family. The clinical features are adolescence-onset muscle weakness and atrophy in distal extremities. This is the first family report of distal-onset DNAJB6 myopathy caused by mutations at this site in China.