Subsequent investigations revealed mutations in Histidyl-TRNA Synthetase 2, Mitochondrial (HARS2), Leucyl-TRNA Synthetase 2, Mitochondrial (LARS2), Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit (CLPP), and Twinkle mtDNA Helicase (TWNK) within the Perrault syndrome framework, utilizing similar genomic methodologies such as linkage analysis or NGS, all crucial for maintaining normal mitochondrial function [48]. This evidence concerns the gene TWNK and Down syndrome.