Document Detail

Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome.
MedLine Citation:
PMID:  17564974     Owner:  NLM     Status:  MEDLINE    
Meckel syndrome (MKS) is a rare autosomal recessive lethal condition characterized by central nervous system malformations, polydactyly, multicystic kidney dysplasia, and ductal changes of the liver. Three loci have been mapped (MKS1-MKS3), and two genes have been identified (MKS1/FLJ20345 and MKS3/TMEM67), whereas the gene at the MKS2 locus remains unknown. To identify new MKS loci, a genomewide linkage scan was performed using 10-cM-resolution microsatellite markers in eight families. The highest heterogeneity LOD score was obtained for chromosome 12, in an interval containing CEP290, a gene recently identified as causative of Joubert syndrome (JS) and isolated Leber congenital amaurosis. In view of our recent findings of allelism, at the MKS3 locus, between these two disorders, CEP290 was considered a candidate, and homozygous or compound heterozygous truncating mutations were identified in four families. Sequencing of additional cases identified CEP290 mutations in two fetuses with MKS and in four families presenting a cerebro-reno-digital syndrome, with a phenotype overlapping MKS and JS, further demonstrating that MKS and JS can be variable expressions of the same ciliopathy. These data identify a fourth locus for MKS (MKS4) and the CEP290 gene as responsible for MKS.
Lekbir Baala; Sophie Audollent; Jéléna Martinovic; Catherine Ozilou; Marie-Claude Babron; Sivanthiny Sivanandamoorthy; Sophie Saunier; Rémi Salomon; Marie Gonzales; Eleanor Rattenberry; Chantal Esculpavit; Annick Toutain; Claude Moraine; Philippe Parent; Pascale Marcorelles; Marie-Christine Dauge; Joëlle Roume; Martine Le Merrer; Vardiella Meiner; Karen Meir; Françoise Menez; Anne-Marie Beaufrère; Christine Francannet; Julia Tantau; Martine Sinico; Yves Dumez; Fiona MacDonald; Arnold Munnich; Stanislas Lyonnet; Marie-Claire Gubler; Emmanuelle Génin; Colin A Johnson; Michel Vekemans; Férechté Encha-Razavi; Tania Attié-Bitach
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-04
Journal Detail:
Title:  American journal of human genetics     Volume:  81     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-13     Completed Date:  2007-09-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  170-9     Citation Subset:  IM    
Université René Descartes et INSERM U-781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.
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MeSH Terms
Abnormalities, Multiple / genetics*,  pathology
Antigens, Neoplasm / genetics*
Brain / abnormalities*
DNA Mutational Analysis
Liver / abnormalities*,  pathology
Lod Score
Multicystic Dysplastic Kidney / genetics*,  pathology
Neoplasm Proteins / genetics*
Polydactyly / genetics*
Portal System / abnormalities*
Grant Support
R01 NS039818-09/NS/NINDS NIH HHS
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cep290 protein, human; 0/Neoplasm Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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