Correlation of MLASA2 Clinical Phenotype and Survival with Mt-TyrRS Protein Damage: Linking Systematic Review, Meta-Analysis and 3D Hotspot Mapping.

ABSTRACT: Myopathy, Lactic Acidosis, and Sideroblastic Anemia type 2 (MLASA2) is a rare mitochondrial disorder caused by pathogenic variants (PVs) in the YARS2 gene (which encodes the Mt-TyrRS protein. We performed a comprehensive clinical-molecular synthesis by integrating a systematic review and meta-analysis of all published MLASA2 cases with survival modeling and three-dimensional structural mapping. Across the aggregated cohort, anemia (88.6%), sideroblastic phenotype (85.7%), and lactic acidosis (82.9%) were the most prevalent phenotypes. Fifteen PVs were identified, dominated by p.(Phe52Leu) (29.4%). Survival estimates were 94.1% at 10 years, 70.7% at 30 years, and 42.4% at 50 years; cardiomyopathy and diagnosis before age 10 were associated with decreased survival. We generated the fi

SUBMITTER: Villafan-Bernal JR 

PROVIDER: S-EPMC12839713 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature