%A González-del Angel,Ariadna %A Bisciglia,Michela %A Vargas-Cañas,Steven %A Fernandez-Valverde,Francisca %A Kazakova,Ekaterina %A Escobar,Rosa Elena %A Romero,Norma B. %A Jardel,Claude %A Rucheton,Benoit %A Stojkovic,Tanya %A Malfatti,Edoardo %D 2019 %J Frontiers in Neurology %C %F %G English %K Mito chondrial genome,cardiomyoapthies,Myopathic conditions,Muscle biopsy,Neuromuscular %Q %R 10.3389/fneur.2019.01049 %W %L %M %P %7 %8 2019-October-04 %9 Case Report %# %! Cardiomyoapthy and radbomyolysis associated to DNA2 mitocondriopathy %* %< %T Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants %U https://www.frontiersin.org/articles/10.3389/fneur.2019.01049 %V 10 %0 JOURNAL ARTICLE %@ 1664-2295 %X 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.