Research Article Unexpected Inheritance Patterns in a Large Cohort of Patients with a Suspected Ciliopathy Aurélie Gouronc , 1 Elodie Javey, 1 Anne-Sophie Leuvrey, 1 Elsa Nourisson, 1 Sylvie Friedmann, 1 Valérie Reichert, 1 Nicolas Derive, 2 Christine Francannet, 3 Boris Keren, 2,4 Jonathan Lévy, 5 Marc Planes, 6 Lyse Ruaud, 5,7 Jeanne Amiel, 8 Hélène Dollfus , 9,10,11 Sophie Scheidecker , 1,9 and Jean Muller 1,9 1 Genetics Diagnostic Laboratory, Strasbourg University Hospital, Strasbourg, France 2 Medical Biology Laboratory SeqOIA-PFMG2025, Paris, France 3 Medical Genetics Service, Clermont-Ferrand University Hospital, Clermont-Ferrand, France 4 Genetics Department, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France 5 Genetics Department, Robert Debré University Hospital, APHP Nord, Paris, France 6 Clinical Genetics Service, CHRU Morvan, 29609 Brest, France 7 UMR 1141 NeuroDiderot, Inserm, Paris University, Paris, France 8 Medical Genomics Service for Rare Diseases, Necker-Sick children Hospital, AP-HP, Paris, France 9 Medical Genetics Laboratory, UMRS_1112, Alsace Medical Genetics Institute (IGMA), Strasbourg University and INSERM, Strasbourg, France 10 Medical Genetics Service, Alsace Medical Genetics Institute (IGMA), Strasbourg University Hospital, Strasbourg, France 11 Reference Center for Rare Disorders in Ophthalmic Genetics (CARGO), Filière SENSGENE, Strasbourg University Hospital, Strasbourg, France Correspondence should be addressed to Jean Muller; jeanmuller@unistra.fr Received 8 January 2023; Revised 5 April 2023; Accepted 13 April 2023; Published 9 August 2023 Academic Editor: William Oetting Copyright © 2023 Aurélie Gouronc et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ciliopathies are rare genetic disorders caused by dysfunction of the primary or motile cilia. Their mode of inheritance is mostly autosomal recessive with biallelic pathogenic variants inherited from the parents. However, exceptions exist such as uniparental disomy (UPD) or the appearance of a de novo pathogenic variant in trans of an inherited pathogenic variant. These two genetic mechanisms are expected to be extremely rare, and few data are available in the literature, especially regarding ciliopathies. In this study, we investigated 940 individuals (812 families) with a suspected ciliopathy by Sanger sequencing, high-throughput sequencing and/or SNP array analysis and performed a literature review of UPD and de novo variants in ciliopathies. In a large cohort of 623 individuals (511 families) with a molecular diagnosis of ciliopathy (mainly Bardet-Biedl syndrome and Alström syndrome), we identified five UPD, revealing an inherited pathogenic variant and five pathogenic variants of de novo appearance (in trans of another pathogenic variant). Moreover, from these ten cases, we reported 15 different pathogenic variants of which five are novel. We demonstrated a relatively high prevalence of UPD and de novo variants in a large cohort of ciliopathies and highlighted the importance of identifying such rare genetic events, especially for genetic counseling. Hindawi Human Mutation Volume 2023, Article ID 2564200, 7 pages https://doi.org/10.1155/2023/2564200