Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle |
| |
Authors: | Tallila Jonna Jakkula Eveliina Peltonen Leena Salonen Riitta Kestilä Marjo |
| |
Institution: | 1 National Public Health Institute and Institute for Molecular Medicine Finland, Helsinki 00290, Finland 2 Institute for Molecular Medicine Finland, Finnish Genome Center, University of Helsinki, Helsinki 00014, Finland 3 Department of Medical Genetics, University of Helsinki, Helsinki 00014, Finland 4 The Broad Institute, Boston, MA 02142, USA 5 The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK 6 Department of Medical Genetics, Väestöliitto, Helsinki 00100, Finland |
| |
Abstract: | Meckel syndrome (MKS) is a lethal malformation disorder characterized classically by encephalocele, polycystic kidneys, and polydactyly. MKS is also one of the major contributors to syndromic neural tube defects (NTDs). Recent findings have shown primary cilia dysfunction in the molecular background of MKS, indicating that cilia are critical for early human development. However, even though four genes behind MKS have been identified to date, they elucidate only a minor proportion of the MKS cases. In this study, instead of traditional linkage analysis, we selected 10 nonrelated affected fetuses and looked for the homozygous regions shared by them. Based on this strategy, we identified the sixth locus and the fifth gene, CC2D2A (MKS6), behind MKS. The biological function of CC2D2A is uncharacterized, but the corresponding polypeptide is predicted to be involved in ciliary functions and it has a calcium binding domain (C2). Immunofluorescence staining of patient's fibroblast cells demonstrates that the cells lack cilia, providing evidence for the critical role of CC2D2A in cilia formation. Our finding is very significant not only to understand the molecular background of MKS, but also to obtain additional information about the function of the cilia, which can help to understand their significance in normal development and also in other ciliopathies, which are an increasing group of disorders with overlapping phenotypes. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|