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A novel heterotaxy gene: Expansion of the phenotype of TTC21B ‐spectrum disease
Author(s) -
Strong Alanna,
Li Dong,
Mentch Frank,
Hakonarson Hakon
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62093
Subject(s) - ciliopathy , heterotaxy , primary ciliary dyskinesia , situs inversus , cilium , biology , exome sequencing , genetics , haploinsufficiency , phenotype , ciliopathies , medicine , pathology , anatomy , gene , heart disease , bronchiectasis , lung
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.