current
ELAC2:c.460T>C AND COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 17
current
classified by single submitter
Pathogenic
germline
human
not provided
curation
In a girl, born of consanguineous parents of Arabic descent, with COXPD17 (615440), Haack et al. (2013) identified a homozygous c.460T-C transition in exon 5 of the ELAC2 gene, resulting in a phe154-to-leu (F154L) substitution at a conserved residue in a metallo-beta-lactamase superfamily domain. The mutation was found by exome sequencing and was present at less than 0.2% frequency in 1,846 control exomes and public databases. She presented at age 2 months with poor growth, hypertrophic cardiomyopathy, and lactic acidosis, and died at age 11 months. Biochemical studies showed decreased complex I activity (60% of normal) in skeletal muscle, and there was an accumulation of unprocessed mt-tRNA intermediates in fibroblasts that could be rescued by expression of wildtype ELAC2. Family history revealed that a brother had died of unknown case at age 13 days and a sister had died of dilated hypertrophic cardiomyopathy at age 3 months.
23849775
ELAC2:c.460T>C
NM_018127.6:c.460T>C
NG_015808.1:g.8596T>C
NC_000017.10:g.12917786A>G
NP_060597.4:p.Phe154Leu
F154L
PHE154LEU
17p11
elaC ribonuclease Z 2
ELAC2
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 17
COXPD17
current
Pathogenic
germline
human
not provided
curation
In a girl, born of consanguineous parents of Arabic descent, with COXPD17 (615440), Haack et al. (2013) identified a homozygous c.460T-C transition in exon 5 of the ELAC2 gene, resulting in a phe154-to-leu (F154L) substitution at a conserved residue in a metallo-beta-lactamase superfamily domain. The mutation was found by exome sequencing and was present at less than 0.2% frequency in 1,846 control exomes and public databases. She presented at age 2 months with poor growth, hypertrophic cardiomyopathy, and lactic acidosis, and died at age 11 months. Biochemical studies showed decreased complex I activity (60% of normal) in skeletal muscle, and there was an accumulation of unprocessed mt-tRNA intermediates in fibroblasts that could be rescued by expression of wildtype ELAC2. Family history revealed that a brother had died of unknown case at age 13 days and a sister had died of dilated hypertrophic cardiomyopathy at age 3 months.
23849775
ELAC2, PHE154LEU
PHE154LEU
ELAC2
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 17