Homozygous DNAJB4 deletion revealing myopathy with acute respiratory failure

Homozygous mutations in the DNAJB4 (NM_007034) gene impair HSP40 function, leading to early respiratory failure due to diaphragm involvement and rigid-spine-like characteristics. We describe the case of a 23-year-old male patient who was admitted for acute respiratory failure and motor deficit of the distal upper limbs. Creatine kinase values were elevated (10x upper normal limit), while the pulmonary function tests showed restrictive respiratory syndrome (forced vital capacity at 20% of theoretical values). The deltoid muscle biopsy findings were consistent with myofibrillar myopathy. Genetic analysis by NGS panel sequencing identified a homozygous deletion c.(?_1)_(1014_?)del, p.? (HGVS nomenclature) of the entire DNAJB4 gene, confirmed by qPCR. Both healthy parents exhibited the variant at the heterozygous state. Our results demonstrate that homozygous c.(?1)(1014_?)del, p.? deletion in DNAJB4 leads to a hereditary myopathy, further underscoring the gene's crucial role in muscle maintenance and function.