Updated exome sequencing identified a homozygous TMEM126B variant as the cause of progressive kidney failure and multisystem disease in a 47-year-old male.
Systematic reanalysis of genetic data can identify novel causes of multisystem disease, such as TMEM126B variants in kidney failure and cardiomyopathy.
Graphical abstract illustrating the clinical presentation, molecular mechanism, and diagnostic implications of biallelic TMEM126B variants associated with progressive kidney disease. The case involved a 47-year-old male with childhood exercise intolerance, possible hypertrophic cardiomyopathy, and progressive kidney failure. Initial comprehensive inherited kidney disease panel testing was nondiagnostic; subsequent updated exome sequencing identified a homozygous TMEM126B variant (c.635G>T; p.Gly212Val). TMEM126B encodes a mitochondrial complex I assembly factor, and pathogenic variants impair complex I assembly and mitochondrial function, contributing to multisystem disease including exercise intolerance, kidney disease and cardiomyopathy. The case highlights the expanding phenotypic spectrum associated with TMEM126B and the importance of periodic gene panel updates and systematic reanalysis to improve diagnostic yield and patient care.
Hammond et al. (Thu,) conducted a letter in Progressive kidney failure and multisystem disease (n=1). Biallelic TMEM126B variants was evaluated on Identification of genetic cause. Updated exome sequencing identified a homozygous TMEM126B variant as the cause of progressive kidney failure and multisystem disease in a 47-year-old male.