A new mutation in the mitochondrial tRNAProgene associated with early-onset neuromuscular phenotype and ragged-red fibers.
An 11-year-old boy with psychomotor delay, exercise intolerance, ptosis and growth delay had a muscle biopsy showing typical mitochondrial alterations (60% of ragged-red fibers and 90% of cytochrome-c oxidase-deficient fibers). Next-generation sequencing revealed a novel heteroplasmic mutation (m.15958A>T) in the MTTP gene that encodes tRNAPro. The mutation was not present in the accessible non-muscle tissues of the patient's asymptomatic mother. Mutations in the rarely affected MTTP gene are responsible for different clinical presentations. We report the third early-onset case associated with a mutation in this gene. The severity of myopathy is likely related to the high mutation rate (96%) found in the patient's muscle. The clinical heterogeneity associated with MTTP mutations illustrates the value of the next-generation sequencing in routine diagnosis of mitochondrial diseases.
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France.
Godelieve
G
Morel
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France.
Sylvie
S
Bannwarth
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France.
Annabelle
A
Chaussenot
Department of Neuropediatrics, Timone Hospital, Marseille Teaching Hospital, France.
Aline
A
Cano
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France.
Konstantina
K
Fragaki
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France.
Samira
S
Ait-El-Mkadem
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France.
Cecile
C
Rouzier
Department of Neuropathology, Timone Hospital, Marseille Teaching Hospital, France.
Andre Maues
AM
De Paula
Department of Neuropediatrics, Timone Hospital, Marseille Teaching Hospital, France.
Brigitte
B
Chabrol
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France. Electronic address: paquis@hermes.unice.fr.
Veronique
V
Paquis-Flucklinger
D002648:Child; D004272:DNA, Mitochondrial; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D012361:RNA, Transfer, Pro / Q000235:genetics*
D004272:DNA, Mitochondrial; D012361:RNA, Transfer, Pro
MTTP gene; Mitochondrial myopathy; NGS; Neuromuscular disease; New mutation; mtDNA