Journal article

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling

Thuy-Linh Le, Yunia Sribudiani, Xiaomin Dong, Celine Huber, Chelsea Kois, Genevieve Baujat, Christopher T Gordon, Valerie Mayne, Louise Galmiche, Valerie Serre, Nicolas Goudin, Mohammed Zarhrate, Christine Bole-Feysot, Cecile Masson, Patrick Nitschke, Frans W Verheijen, Lynn Pais, Anna Pelet, Simon Sadedin, John A Pugh Show all

The American Journal of Human Genetics | CELL PRESS | Published : 2020


The evolutionarily conserved hedgehog (Hh) pathway is essential for organogenesis and plays critical roles in postnatal tissue maintenance and renewal. A unique feature of the vertebrate Hh pathway is that signal transduction requires the primary cilium (PC) where major pathway components are dynamically enriched. These factors include smoothened (SMO) and patched, which constitute the core reception system for sonic hedgehog (SHH) as well as GLI transcription factors, the key mediators of the pathway. Here, we report bi-allelic loss-of-function variations in SMO in seven individuals from five independent families; these variations cause a wide phenotypic spectrum of developmental anomalies ..

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Awarded by "Agence Nationale de la Recherche'' (ANR)

Awarded by Fondation Maladies Rares

Awarded by ANR under the "Investissements d'avenir'' program

Awarded by second "Investissements d'Avenir'' program

Funding Acknowledgements

We are grateful to the affected individuals and their families for their participation. We thank Marc Le Loch for help with targeted resequencing and Megan Cho for scientific networking. This work was supported by grants from the "Agence Nationale de la Recherche'' (ANR) to S.T. (ANR-17-CE16-0003-01), MSDAvenir (DevoDecode project), and the "Fondation Maladies Rares" (HTS-RD-I20140502). T.L.L. is supported by the French Excellence Program of the French Embassy in Vietnam and the "Fondation pour la Recherche Medicale'' (PhD program). The Imagine Institute is supported by state funding from the ANR under the "Investissements d'avenir'' program (ANR-10-IAHU-01) and as part of the second "Investissements d'Avenir'' program (ANR-17-RHUS-0002). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program.