CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation

Soumaya Mougou-Zerelli, Sophie Thomas, Emmanuelle Szenker, Sophie Audollent, Nadia Elkhartoufi, Candice Babarit, Stéphane Romano, Rémi Salomon, Jeanne Amiel, Chantal Esculpavit, Marie Gonzales, Estelle Escudier, Bruno Leheup, Philippe Loget, Sylvie Odent, Joëlle Roume, Marion Gérard, Anne Lise Delezoide, Suonavy Khung, Sophie PatrierMarie Pierre Cordier, Raymonde Bouvier, Jéléna Martinovic, Marie Claire Gubler, Nathalie Boddaert, Arnold Munnich, Férechté Encha-Razavi, Enza Maria Valente, Ali Saad, Sophie Saunier, Michel Vekemans, Tania Attié-Bitach

Research output: Contribution to journalArticlepeer-review


Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic "molar tooth sign" (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozygous splice mutation with a founder effect was reported in the CC2D2A gene in Finnish fetuses with MKS, defining the 6th locus for MKS. Shortly thereafter, CC2D2A mutations were also reported in JBS. The analysis of the CC2D2A gene in our series of MKS fetuses, identified 14 novel truncating mutations in 11 cases. These results confirm the involvement of CC2D2A in MKS and reveal a major contribution of CC2D2A to the disease. We also identified three missense CC2D2A mutations in two JBS cases. Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype-genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS.

Original languageEnglish
Pages (from-to)1574-1582
Number of pages9
JournalHuman Mutation
Issue number11
Publication statusPublished - Nov 2009


  • CC2D2A
  • Ciliopathy
  • JBS
  • Joubert syndrome
  • Meckel-Gruber syndrome
  • MKS

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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