TY - JOUR T1 - Mutations in <em>CEP120</em> cause Joubert syndrome as well as complex ciliopathy phenotypes JF - Journal of Medical Genetics JO - J Med Genet SP - 608 LP - 615 DO - 10.1136/jmedgenet-2016-103832 VL - 53 IS - 9 AU - Susanne Roosing AU - Marta Romani AU - Mala Isrie AU - Rasim Ozgur Rosti AU - Alessia Micalizzi AU - Damir Musaev AU - Tommaso Mazza AU - Lihadh Al-gazali AU - Umut Altunoglu AU - Eugen Boltshauser AU - Stefano D'Arrigo AU - Bart De Keersmaecker AU - Hülya Kayserili AU - Sarah Brandenberger AU - Ichraf Kraoua AU - Paul R Mark AU - Trudy McKanna AU - Joachim Van Keirsbilck AU - Philippe Moerman AU - Andrea Poretti AU - Ratna Puri AU - Hilde Van Esch AU - Joseph G Gleeson AU - Enza Maria Valente Y1 - 2016/09/01 UR - http://jmg.bmj.com/content/53/9/608.abstract N2 - Background Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene.Methods Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent next-generation sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes.Results We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype.Conclusion Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype–phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies. ER -