AUTHOR=González-del Angel Ariadna , Bisciglia Michela , Vargas-Cañas Steven , Fernandez-Valverde Francisca , Kazakova Ekaterina , Escobar Rosa Elena , Romero Norma B. , Jardel Claude , Rucheton Benoit , Stojkovic Tanya , Malfatti Edoardo
TITLE=Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants
JOURNAL=Frontiers in Neurology
VOLUME=10
YEAR=2019
URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01049
DOI=10.3389/fneur.2019.01049
ISSN=1664-2295
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.