PT  - JOURNAL ARTICLE
AU  - Harion, Madeleine
AU  - Qebibo, Leila
AU  - Riquet, Audrey
AU  - Rougeot, Christelle
AU  - Afenjar, Alexandra
AU  - Garel, Catherine
AU  - Louha, Malek
AU  - Lacaze, Emmanuelle
AU  - Audic-Gérard, Frédérique
AU  - Barth, Magali
AU  - Berquin, Patrick
AU  - Bonneau, Dominique
AU  - Bourdain, Frédéric
AU  - Busa, Tiffany
AU  - Colin, Estelle
AU  - Cuisset, Jean-Marie
AU  - Des Portes, Vincent
AU  - Dorison, Nathalie
AU  - Francannet, Christine
AU  - Héron, Bénédicte
AU  - Laroche, Cécile
AU  - Lebrun, Marine
AU  - Métreau, Julia
AU  - Odent, Sylvie
AU  - Pasquier, Laurent
AU  - Trujillo, Yaumara Perdomo
AU  - Perrin, Laurine
AU  - Pinson, Lucile
AU  - Rivier, François
AU  - Sigaudy, Sabine
AU  - Thauvin-Robinet, Christel
AU  - Louvier, Ulrike Walther
AU  - Labayle, Olivier
AU  - Rodriguez, Diana
AU  - Valence, Stéphanie
AU  - Burglen, Lydie
TI  - New insights into <em>CC2D2A</em>-related Joubert syndrome
AID  - 10.1136/jmg-2022-108754
DP  - 2023 Jun 01
TA  - Journal of Medical Genetics
PG  - 578--586
VI  - 60
IP  - 6
4099  - http://jmg.bmj.com/content/60/6/578.short
4100  - http://jmg.bmj.com/content/60/6/578.full
SO  - J Med Genet2023 Jun 01; 60
AB  - Purpose In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes, CC2D2A.Methods We selected 53 patients with pathogenic variants on CC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature.Results Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype–phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype.Conclusion This study contradicts previous literature stating an association between CC2D2A-related JS and ventriculomegaly. Our study implies that CC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.Data sharing not applicable as no datasets generated and/or analysed for this study.