A novel heterotaxy gene: Expansion of the phenotype of TTC21B-spectrum disease.

• 影响指数: 2.578
• 发表时间: 04 2021
• 来源期刊: Am J Med Genet A
• DOI: 10.1002/ajmg.a.62093
• PMID: 33547761
• 文章类型: Case Reports
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Strong A,Li D,Mentch F,Hakonarson H

关键词: IFT139; TTC21B; cilia; ciliopathy; heterotaxy

Mesh: Abnormalities, Multiple / genetics pathology; Cerebellum / abnormalities pathology; Child; Ciliary Motility Disorders / complications genetics pathology; Eye Abnormalities / complications genetics pathology; Genetic Predisposition to Disease; Glomerulosclerosis, Focal Segmental / complications genetics pathology; Heterotaxy Syndrome / complications genetics pathology; Humans; Kidney / metabolism pathology; Kidney Diseases, Cystic / complications congenital genetics pathology; Kidney Transplantation; Male; Microtubule-Associated Proteins / genetics; Retina / abnormalities pathology; Whole Exome Sequencing

Abstract

TTC21B encodes the protein IFT139, a critical component of the retrograde transport system within the primary cilium. Biallelic, pathogenic TTC21B variants are associated with classic ciliopathy syndromes, including nephronophthisis, Jeune asphyxiating thoracic dystrophy, and Joubert Syndrome, with ciliopathy-spectrum traits such as biliary dysgenesis, primary ciliary dyskinesia, and situs inversus, and also with focal segmental glomerulosclerosis. We report a 9-year-old male with focal segmental glomerulosclerosis requiring kidney transplant, primary ciliary dyskinesia, and biliary dysgenesis, found by research-based exome sequencing to have biallelic pathogenic TTC21B variants. A sibling with isolated heterotaxy was found to harbor the same variants. This case highlights the phenotypic spectrum and unpredictable manifestations of TTC21B-related disease, and also reports the first association between TTC21B and heterotaxy, nominating TTC21B as an important new heterotaxy gene.