Frontiers in Neurology (Oct 2019)
Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants
Abstract
Objectives: To report two novel DNA2 gene mutations causing early onset myopathy with cardiac involvement and late onset mitochondriopathy with rhabdomyolysis.Methods: We performed detailed clinical, muscle histopathology and molecular studies including mitochondrial gene NGS analysis in two patients (Patient 1 and 2), a mother and her son, belonging to a Mexican family, and a third sporadic French patient.Results: Patient 1 and 2 presented with an early onset myopathy associated with ptosis, velopharyngeal weakness, and cardiac involvement. Patient 3 presented rhabdomyolysis unmasking a mitochondrial disease characterized by a sensorineural hearing loss, ptosis, and lipomas. Muscle biopsies performed in all patients showed variable mitochondrial alterations. Patient 3 had multiple mtDNA deletion in his muscle. Genetic studies revealed a novel heterozygous frameshift mutation in DNA2 gene (c.2346delT p.Phe782Leufs*3) in P1 and P2, and a novel heterozygous missense mutation in DNA2 gene (c.578T>C p.Leu193Ser) in the P3.Conclusions: To date only few AD cases presenting either missense or truncating DNA2 variants have been reported. None of them presented with a cardiac involvement or rhabdomyolysis. Here we enlarge the genetic and phenotypic spectrum of DNA2-related mitochondrial disorders.
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