Recurrent Single-Nucleotide Insertions in the Mitochondrial Second Light-Strand Promoter Cause Tubulointerstitial Kidney Disease

A research team analyzed mitochondrial DNA (mtDNA) in 33 families with suspected maternal inheritance and found that 18 families (55%) carried disease-associated mtDNA variants. The most common were homoplasmic insertions in the second light-strand promoter (LSP2) in 9 families. Results showed strong maternal transmission: 90% of offspring from affected mothers had reduced kidney function compared to only 6% of offspring from affected fathers. Affected individuals predominantly presented with chronic tubulointerstitial kidney disease, sometimes accompanied by gout. Overall, 109 of 119 genetically affected individuals or at-risk carriers were clinically affected. The research confirms that mtDNA variants are an important cause of familial and sporadic tubulointerstitial kidney disease with previously unexplained etiology.