| Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle. | |
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MedLine Citation:
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PMID: 18513680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jonna Tallila; Eveliina Jakkula; Leena Peltonen; Riitta Salonen; Marjo Kestilä |
Publication Detail:
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Type: Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of human genetics Volume: 82 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-03 Completed Date: 2008-06-27 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 1361-7 Citation Subset: IM |
Affiliation:
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National Public Health Institute, Institute for Molecular Medicine Finland, Helsinki 00290, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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genetics* Base Sequence Cilia / physiology Ciliary Motility Disorders / genetics*, physiopathology DNA, Complementary / genetics Encephalocele / genetics Female Humans Mutation* Neural Tube Defects / genetics Polycystic Kidney Diseases / genetics Polydactyly / genetics Pregnancy Proteins / genetics* Syndrome |
| Grant Support | |
ID/Acronym/Agency:
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P01 ES11253-03/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CC2D2A protein, human; 0/DNA, Complementary; 0/Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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