Loss of function IFT27 variants associated with an unclassified lethal fetal ciliopathy with renal agenesis |
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| Authors: | Chloé Quélin Philippe Loget Lucile Boutaud Nadia Elkhartoufi Joelle Milon Sylvie Odent Mélanie Fradin Florence Demurger Laurent Pasquier Sophie Thomas Tania Attié‐Bitach |
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| Affiliation: | 1. Service de Génétique Clinique, Centre de Référence Maladies Rares CLAD‐Ouest, CHU H?pital Sud, Rennes, France;2. Service d'Anatomopathologie, CHU Pontchaillou, Rennes, France;3. Unité d'Embryofoetopathologie, Service d'Histologie‐Embryologie‐Cytogénétique, H?pital Necker‐Enfants Malades, Assistance Publique – H?pitaux de Paris (AP‐HP), Paris, France;4. Inserm U1163, Université Paris Descartes – Sorbonne Paris Cité, Institut Imagine, Paris, France;5. P?le d'imagerie médicale, CHU H?pital Sud, Rennes, France |
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| Abstract: | 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. |
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| Keywords: | ciliopathy IFT27 Pallister– hall syndrome short‐rib polydactyly |
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