Details

Autor(en) / Beteiligte

• Hershkovitz, Tova
• Kurolap, Alina
• Gonzaga-Jauregui, Claudia
• Paperna, Tamar
• Mory, Adi
• Wolf, Sarah E
• Overton, John D
• Shuldiner, Alan R
• Saada, Ann
• Mandel, Hanna
• Baris Feldman, Hagit

Titel

A novel TUFM homozygous variant in a child with mitochondrial cardiomyopathy expands the phenotype of combined oxidative phosphorylation deficiency 4

Ist Teil von

• Journal of human genetics, 2019-06, Vol.64 (6), p.589-595

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Translation of mitochondrial-specific DNA is required for proper mitochondrial function and energy production. For this purpose, an elaborate network of dedicated molecular machinery including initiation, elongation and termination factors exists. We describe a patient with an unusual phenotype and a novel homozygous missense variant in TUFM (c.344A>C; p.His115Pro), encoding mtDNA translation elongating factor Tu (EFTu). To date, only four patients have been reported with bi-allelic mutations in TUFM, leading to combined oxidative phosphorylation deficiency 4 (COXPD4) characterized by severe early-onset lactic acidosis and progressive fatal infantile encephalopathy. The patient presented here expands the phenotypic features of TUFM-related disease, exhibiting lactic acidosis and dilated cardiomyopathy without progressive encephalopathy. This warrants the inclusion of TUFM in differential diagnosis of metabolic cardiomyopathy. Cases that further refine genotype-phenotype associations and characterize the molecular basis of mitochondrial disorders allow clinicians to predict disease prognosis, greatly impacting patient care, as well as provide families with reproductive planning options.