Identification of GDNF Gene Sequence Variations in Patients with Medullary Sponge Kidney Disease
| Autor: | Rossella Torregrossa, L. Artifoni, Antonio Lupo, Cataldo Abaterusso, Antonia Fabris, Alessia Gozzini, Annalisa Tanini, Dorella Del Prete, Nicola Marchionna, Angela D'Angelo, Franca Anglani, Giovanni Gambaro, Rosalba Cristofaro |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology Heredity Epidemiology DNA Mutational Analysis Critical Care and Intensive Care Medicine Loss of heterozygosity Gene Frequency Glial cell line-derived neurotrophic factor Settore MED/14 - NEFROLOGIA Medicine GDNF gene hypercalciuria education.field_of_study biology Reverse Transcriptase Polymerase Chain Reaction Exons Pedigree Phenotype Italy Proto-Oncogene Proteins c-ret Nephrology Female Nephrocalcinosis Heterozygote medicine.medical_specialty Population Medullary sponge kidney Humans MSK Genetic Predisposition to Disease Glial Cell Line-Derived Neurotrophic Factor Allele education Allele frequency MEDULLARY SPONGE KIDNEY GDNF GENE Transplantation Medullary Sponge Kidney business.industry Genetic Variation Original Articles renal stone medicine.disease Introns body regions Case-Control Studies biology.protein Cancer research business Biomarkers |
| Zdroj: | Clinical Journal of the American Society of Nephrology. 5:1205-1210 |
| ISSN: | 1555-9041 |
| DOI: | 10.2215/cjn.07551009 |
| Popis: | Background and objectives: Medullary sponge kidney (MSK) is a rare nephropathy characterized by cystic anomalies of precalyceal ducts, nephrocalcinosis, renal stones, and tubule dysfunctions. Its association with various malformations and cases of familial aggregation supports the conviction that genetic factors are involved, but no genetic studies have been conducted to date. It is hypothesized that MSK is due to a disruption at the “ureteric bud/metanephric blastema” interface caused by critical developmental genes functioning abnormally. Design, setting, participants, & measurements: Fifty-five apparently sporadic MSK patients were analyzed by direct DNA sequencing of all exons and exon-intron boundaries of glial cell-derived neurotrophic factor (GDNF) gene and rearranged during transfection (RET) gene, which have a leading role in renal development. Results: Two novel variants were found in heterozygosity in the MSK case population: GDNF{ENST00000344622}:c.−45G>C and c.−27+18G>A in a putative binding domain for paired-box 2 transcription factor. As a whole, eight patients showed these variations: four patients carried the c.[−45G>C; −27+18G>A] complex allele, and the others had the c.−27+18G>A alone. A case-control study revealed that these two alleles were significantly associated with MSK. Five of the eight cases were found to be familial, and the allele variants cosegregated with the disease in a seemingly dominant pattern of inheritance. Patients revealed no mutations in the RET gene. Conclusions: This is the first report identifying GDNF gene sequence variations in patients with MSK and suggesting a role for this gene in the pathogenesis of some cases of the disease. |
| Databáze: | OpenAIRE |
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