Mitochondrial disorder due to a defect in mitochondrial protein synthesis
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare neurologic disease
Comment:
A mutation in the large mitochondrial ribosomal protein MRPL3 (= COXPD8) in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency has been identified. Affected sibs were compound heterozygotes for a missense MRPL3 mutation (P317R) and a largescale deletion, inherited from the mother and the father, respectively. These mutations were shown to alter ribosome assembly and cause a mitochondrial translation deficiency in cultured skin fibroblasts resulting in an abnormal assembly of several complexes of the respiratory chain (PMID:21786366).
Galmiche et al. (2011) reported a nonconsanguineous French family in which 4 sibs had a severe mitochondrial disorder. After normal growth and development in the first few months of life, the patients presented at about 6 months of ... Galmiche et al. (2011) reported a nonconsanguineous French family in which 4 sibs had a severe mitochondrial disorder. After normal growth and development in the first few months of life, the patients presented at about 6 months of age with failure to thrive and poor feeding. Hypertrophic cardiomyopathy was diagnosed at 9 to 11 months of age, and resulted in death in 2 patients at ages 17 and 15 months, respectively. Other features included hepatomegaly and psychomotor retardation. Laboratory studies showed increased plasma lactate and alanine, as well as abnormal liver enzymes. Detailed studies on patient fibroblasts and muscle samples showed a combined decrease in activity of mitochondrial respiratory complexes I, III, IV, and V, with a mild decrease in complex II. BN-PAGE analysis showed a decrease in fully assembled complexes I, IV, and V, whereas complex II was normal.
Exome sequencing of 1 of the patients in the family reported by Galmiche et al. (2011) revealed a heterozygous mutation in the MRPL3 gene (P317R; 607118.0001) inherited from the unaffected mother. The patient was also found to carry ... Exome sequencing of 1 of the patients in the family reported by Galmiche et al. (2011) revealed a heterozygous mutation in the MRPL3 gene (P317R; 607118.0001) inherited from the unaffected mother. The patient was also found to carry a 255-kb deletion resulting in loss of the MRPL3, TMCC1, and TRH (613879) genes inherited from the unaffected father; deletion of the latter 2 genes was not thought to affect the phenotype.