Gene. 2026 Mar 16:150106. doi: 10.1016/j.gene.2026.150106. Online ahead of print.
ABSTRACT
BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic disorder characterized by tubular damage and interstitial fibrosis, with inescapable progression to end-stage renal disease. SEC61A1-related ADTKD has long been neglected and underrecognized because of its rarity, insidious onset and variable clinical manifestations.
RESULTS: A 13-year-old boy was referred to the pediatric nephrology clinic due to renal insufficiency, which had been found unexpectedly while visiting the hospital because of growth retardation. He had normocytic normochromic anemia since early childhood and was recently found to have agranulocytosis. The evaluation suggested elevated serum creatinine, hyperuricemia, bland urinary sediment, the absence of proteinuria, and renal cysts. A novel de novo heterozygous missense variant in SEC61A1, Ser71Pro, was found. So far fifteen patients with SEC61A1-related ADTKD have been reported, most of whom presented with early-onset chronic kidney disease and hyperuricemia. The extrarenal features included growth retardation, hematological abnormalities, cognitive impairment, and immunological abnormalities. There is no specific treatment for the SEC61A1-related ADTKD. Most reported patients survived to adulthood with supportive treatment.
CONCLUSIONS: This is the first case of SEC61A1-related ADTKD of Chinese origin, extending its phenotype and mutation spectrum. The diagnosis of SEC61A1-related ADTKD should be considered in patients with early-onset or familial chronic kidney disease, hematological abnormalities and growth retardation, and mutation analysis of SEC61A1 is needed.
PMID:41850665 | DOI:10.1016/j.gene.2026.150106