New insights into CC2D2A-related Joubert syndrome.

  • Madeleine Harion
  • Leila Qebibo
  • Audrey Riquet
  • Christelle Rougeot
  • Alexandra Afenjar
  • Catherine Garel
  • Malek Louha
  • Emmanuelle Lacaze
  • Frédérique Audic-Gérard
  • Magali Barth
  • Patrick Berquin
  • Dominique Bonneau
  • Frédéric Bourdain
  • Tiffany Busa
  • Estelle Colin
  • Jean-Marie Cuisset
  • Vincent Des Portes
  • Nathalie Dorison
  • Christine Francannet
  • Bénédicte Héron
  • Cécile Laroche
  • Marine Lebrun
  • Julia Métreau
  • Sylvie Odent
  • Laurent Pasquier
  • Yaumara Perdomo Trujillo
  • Laurine Perrin
  • Lucile Pinson
  • François Rivier
  • Sabine Sigaudy
  • Christel Thauvin-Robinet
  • Ulrike Walther Louvier
  • Olivier Labayle
  • Diana Rodriguez
  • Stéphanie Valence
  • Lydie Burglen

Source: J Med Genet

Publié le


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.