New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies.

Tiina Ojala, Padmini Polinati, Tuula Manninen, Anita Hiippala, Jukka Rajantie, Riitta Karikoski, Anu Suomalainen, Tiina Tyni

Department of Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. tiina.h.ojala@hus.fi

Pediatric research 2012 Oct

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We report a new mutation in the human DNAJC19 gene that causes early onset dilated cardiomyopathy syndrome (DCMA). Two brothers of Finnish origin presented with an unusual combination of early onset dilated cardiomyopathy syndrome, a disease which was associated with cardiac noncompaction, microcytic anemia, ataxia, male genital anomalies and methylglutaconic aciduria type V. Suspicion of a DCMA syndrome prompted sequencing of the human DNAJC19 gene. Sequencing of the human DNAJC19 gene showed a homozygous single nucleotide (A) deletion in alanine 63 coding triplet in exon 6, which does not immediately cause amino acid change but leads 11 amino acids later to a stop codon and to premature termination of the peptide. This DNAJC19 protein is located in the inner mitochondrial membrane and has been shown to function as a mitochondrial chaperone. This is the first clinical report of DCMA syndrome, a human DNAJC19 deficiency, that is related to cases of severe dilated cardiomyopathy diagnosed in Europe. DNAJC19 deficiency causes a relatively specific finding in urinary organic acid analysis (methylglutaconic aciduria type V), which together with the clinical features of the ensuing cardiac disease, allows for effective screening before undertaking molecular genetic analysis.

Citation

Tiina Ojala, Padmini Polinati, Tuula Manninen, Anita Hiippala, Jukka Rajantie, Riitta Karikoski, Anu Suomalainen, Tiina Tyni. New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies. Pediatric research. 2012 Oct;72(4):432-7