Novel Variant in Muscular Dystrophy: Identification by Whole Genome Sequencing and Quad Analysis.

BACKGROUND

The phenotypic spectrum of muscle disease ranges widely from elevated creatine kinase (CK) levels in the serum of asymptomatic individuals to progressive muscular dystrophy. Due to overlapping clinical features among muscular dystrophies, the diagnosis of muscle disease is established by molecular genetic tests. Early diagnosis is crucial for the clinical management of symptoms and to mitigate cardiac and musculoskeletal complications.

METHODS

Quad-joint analysis was performed on whole genome sequencing (WGS) data obtained from an 18-year-old female with mild myalgia and elevated CK and her unaffected parents and sister. The phenotype-driven analysis was performed to prioritize genomic alterations related to the phenotype. The zygosity-based analysis investigated compound heterozygous and status for all variants.

RESULTS

The quad-joint WGS analysis revealed a novel pathogenic heterozygous variant, :c.1770_1773del (p.Phe593Metfs15), that was paternally inherited. A second and known pathogenic heterozygous variant, :c.148C>T (p.Arg50), was also present that was maternally inherited. The genome finding led to the diagnosis of autosomal recessive muscle disease and an early personalized clinical management for the patient regarding her cardiac and musculoskeletal health.

CONCLUSIONS

This is the first report of the :c.1770_1773del variant in the literature. This report highlights the spectrum of muscle disease and describes the role of quad-joint WGS in the early diagnosis and preventive clinical management of muscle disease.