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

Soumaya Mougou-Zerelli 1, 2 Sophie Thomas 1 Emmanuelle Szenker 1 Sophie Audollent 3 Nadia Elkhartoufi 3 Candice Babarit 1 Stéphane Romano 4 Rémi Salomon 5 Jeanne Amiel 1, 3 Chantal Esculpavit 5 Marie Gonzales 6 Estelle Escudier 7 Bruno Leheup 8 Philippe Loget 9 Sylvie Odent 10 Joëlle Roume 11 Marion Gérard 12 Anne-Lise Delezoide 13 Suonavy Khung 13 Sophie Patrier 6 Marie-Pierre Cordier 14 Raymonde Bouvier 15 Jéléna Martinovic 3 Marie-Claire Gubler 5 Nathalie Boddaert 16, 17 Arnold Munnich 1, 3 Férechté Encha-Razavi 1, 3 Enza Maria Valente 18, 19 Ali Saad 2 Sophie Saunier 5 Michel Vekemans 1, 3 Tania Attié-Bitach 1, 3, *
* Corresponding author
1 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
2 Service de Cytogénétique, Génétique moléculaire et Biologie de la reproduction
3 Service de Génétique Médicale [CHU Necker]
4 Service de pédiatrie générale [CHU Necker]
5 Neuropathies héréditaires et rein en développement
6 Service de génétique et embryologie médicales [CHU Trousseau]
7 Physiopathologie des maladies génétiques d'expression pédiatrique
8 Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy]
9 Cabinet d'Anatomie et Cytologie Pathologiques Richier
10 Service de génétique clinique
11 Service de génétique médicale
12 Service de génétique médicale
13 Service de Biologie du Développement
14 Service de Génétique
15 Centre de pathologie Est
16 Service de radiologie pédiatrique [CHU Necker]
17 Imagerie Cerebrale en Psychiatrie
18 Istituto CSS Mendel
19 Department of Medical and Surgical Pediatrics
Abstract : 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.
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https://www.hal.inserm.fr/inserm-00420359
Contributor : Hervé de Villemeur <>
Submitted on : Monday, September 28, 2009 - 4:59:02 PM
Last modification on : Thursday, December 10, 2020 - 3:43:29 AM

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Soumaya Mougou-Zerelli, Sophie Thomas, Emmanuelle Szenker, Sophie Audollent, Nadia Elkhartoufi, et al.. CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation.. Human Mutation, Wiley, 2009, 30 (11), pp.1574-82. ⟨10.1002/humu.21116⟩. ⟨inserm-00420359⟩

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