Disease #00572
| Official abbreviation |
MLASA3 |
| Name |
500011 MYOPATHY, LACTIC ACIDOSIS, AND SIDEROBLASTIC ANEMIA 3; MLASA3 |
| OMIM ID |
500011 |
| Human Phenotype Ontology Project (HPO) |
HPO |
| Individuals reported having this disease |
0 |
| Phenotype entries for this disease |
0 |
| Associated with 1 gene |
MT-ATP6 |
| Associated tissues |
- |
| Disease features |
Evidence that myopathy, lactic acidosis, and sideroblastic anemia-3 (MLASA3) is caused by heteroplasmic mutation in the mitochondrial-encoded ATP6 gene (MTATP6; 516060). One such patient has been reported.
▼ Description
MLASA3 is a severe mitochondrial disorder with early infantile presentation of transfusion-dependent sideroblastic anemia in the setting of failure to thrive, hearing loss, epilepsy, stroke-like episodes, and severe developmental delay (summary by Burrage et al., 2014).
For a general phenotypic description and a discussion of genetic heterogeneity of MLASA, see MLASA1 (600462) |
| Remarks |
▼ Molecular Genetics
Using Sanger sequencing of the mitochondrial genome in a patient with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia, Burrage et al. (2014) detected an apparently homoplasmic novel variant in the MTATP6 gene (m.8969G-A, S148N; 516060.0012). Next-generation sequencing confirmed the presence of this variant at 96% and 88% heteroplasmy in the proband's blood and muscle specimens, respectively, and did not detect the variant in his mother's blood sample. Two other apparently homoplasmic rare variants were also detected in the proband's muscle and blood specimens; these variants had been reported in the mtDB, occurred at evolutionarily nonconserved positions, and were present in the proband's asymptomatic mother, and so were considered unlikely to be causative. Functional studies using a patient-derived skin fibroblast line showed a profound reduction in oligomycin-sensitive respiration compared to control, consistent with a defect in mitochondrial complex V function. Whole-exome sequencing of relevant nuclear genes detected no pathogenic variants |
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