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Loss of function IFT27 variants associated with an unclassified lethal fetal ciliopathy with renal agenesis
Author(s) -
Quélin Chloé,
Loget Philippe,
Boutaud Lucile,
Elkhartoufi Nadia,
Milon Joelle,
Odent Sylvie,
Fradin Mélanie,
Demurger Florence,
Pasquier Laurent,
Thomas Sophie,
AttiéBitach Tania
Publication year - 2018
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.38685
Subject(s) - ciliopathy , ciliopathies , cilium , intraflagellar transport , polydactyly , biology , phenotype , genetics , bardet–biedl syndrome , joubert syndrome , renal agenesis , ciliogenesis , gene , kidney , mutant
Ciliopathies comprise a group of clinically heterogeneous and overlapping disorders with a wide spectrum of phenotypes ranging from prenatal lethality to adult‐onset disorders. Pathogenic variants in more than 100 ciliary protein‐encoding genes have been described, most notably those involved in intraflagellar transport (IFT) which comprises two protein complexes, responsible for retrograde (IFT‐A) and anterograde transport (IFT‐B). Here we describe a fetus with an unclassified severe ciliopathy phenotype including short ribs, polydactyly, bilateral renal agenesis, and imperforate anus, with compound heterozygosity for c.118_125del, p.(Thr40Glyfs*11) and a c.352 +1G > T in IFT27 , which encodes a small GTPase component of the IFT‐B complex. We conclude that bilateral renal agenesis is a rare feature of this severe ciliopathy and this report highlights the phenotypic overlap of Pallister–Hall syndrome and ciliopathies. The phenotype in patients with IFT27 gene variants is wide ranging from Bardet–Biedl syndrome to a lethal phenotype.