OFD1, the Gene Mutated in Oral-Facial-Digital Syndrome Type 1, Is Expressed in the Metanephros and in Human Embryonic Renal Mesenchymal Cells
| Autor: | Giovanna Giorgio, Karen L. Price, Sue Malcolm, Sally Feather, Mary Porteous, Dian Donnai, Paul J.D. Winyard, Brunella Franco, Leila Romio, Adrian S. Woolf, Victoria Wright |
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| Rok vydání: | 2003 |
| Předmět: |
Pathology
medicine.medical_specialty Cellular differentiation Biology Kidney Transfection Cell Line Frameshift mutation Mesoderm Gene product Metanephros Gene expression medicine Polycystic kidney disease Humans Missense mutation Northern blot Frameshift Mutation Gene Expression Regulation Developmental Proteins Cell Differentiation General Medicine Orofaciodigital Syndromes medicine.disease Molecular biology Nephrology RNA Splice Sites Signal Transduction |
| Zdroj: | Journal of the American Society of Nephrology. 14:680-689 |
| ISSN: | 1046-6673 |
| DOI: | 10.1097/01.asn.0000054497.48394.d2 |
| Popis: | Oral-facial-digital syndrome type 1 (OFD1) causes polycystic kidney disease (PKD) and malformations of the mouth, face and digits. Recently, a gene on Xp22, OFD1, was reported to be mutated in a limited set of OFD1 patients. This study describes mutation analysis in six further OFD1 families. Additionally, gene expression was sought in human development. In two OFD1 kindreds affected by PKD, a frameshift mutation and a splice-site mutation were detected. In four apparently sporadic cases, three frameshift and a missense mutation were found. Using RT-PCR of RNA from first-trimester normal human embryos, both alternative splice forms of mRNA (OFD1a and OFD1b) were found to be widely expressed in organogenesis. Northern blot detected OFD1 mRNA in metanephros, brain, tongue, and limb, all organs affected in the syndrome. A polyclonal antibody directed to a C-terminal OFD1a epitope detected a 120-kD protein in the metanephros and in human renal mesenchymal cell lines. In normal human embryos, OFD1a immunolocalized to the metanephric mesenchyme, oral mucosa, nasal and cranial cartilage, and brain. Moreover, using normal human renal mesenchymal cell lines, the immunoreactive protein colocalized with gamma-tubulin, suggesting that OFD1 is associated with the centrosome. First, it is concluded that OFD1 mutations would generally be predicted to result in unstable transcripts or nonfunctional proteins. Second, OFD1 is expressed in human organogenesis; on the basis of the metanephric expression pattern, the results suggest that OFD1 plays a role in differentiation of metanephric precursor cells. |
| Databáze: | OpenAIRE |
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