Alternative titles; symbols
DO: 580;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q21.2 | {Nephrolithiasis, uric acid, susceptibility to} | 605990 | 3 | ZNF365 | 607818 |
A number sign (#) is used with this entry because of evidence that susceptibility to the multifactorial disorder uric acid nephrolithiasis is conferred by variation in the ZNF365 gene (607818) on chromosome 10q21.
Ombra et al. (2001) studied a small, isolated founder population in Talana, a Sardinian village where the prevalence of nephrolithiasis is higher than that in Western populations. By multistep linkage and allele-sharing analyses, they identified 2 chromosome regions that may harbor susceptibility genes for uric acid stones. The strongest evidence was observed on 10q21-q22, where a lod score of 3.07 was obtained for D10S1652 under an affected-only dominant model and a lod score of 3.90 was obtained using a dominant pseudomarker assignment. The localization was supported also by multipoint allele-sharing statistics and by haplotype analysis of familial cases and of unrelated affected subjects collected from the isolate. Suggestive evidence was obtained in an approximately 20-cM region on 20q13.1-q13.3 by multipoint nonparametric analysis.
To refine the critical mapping region and to identify the susceptibility gene for uric acid nephrolithiasis, Gianfrancesco et al. (2003) extended the UAN analysis of Ombra et al. (2001) to severely affected subjects from Talana. They confirmed the involvement of the 10q region in the disorder through identical-by-descent sharing and autozygosity mapping, and refined the critical region to an interval of approximately 67 kb by linkage disequilibrium mapping. By database mining, they determined that a novel gene, ZNF365, overlaps the critical interval. Mutation analysis of the gene showed that an ala62-to-thr mutation in exon 12 (A62T; 607818.0001) of the ZNF365D isoform, which the authors called talanin, was in strong association with UAN (P = 0.0051). Moreover, the mutation modified the secondary structure of the predicted protein, suggesting that it may have a role in UAN etiology. The study of Gianfrancesco et al. (2003) illustrated how a candidate gene for a multifactorial disorder could be identified using a relatively small sample of affected and unaffected subjects.
Gianfrancesco, F., Esposito, T., Ombra, M. N., Forabosco, P., Maninchedda, G., Fattorini, M., Casula, S., Vaccargiu, S., Casu, G., Cardia, F., Deiana, I., Melis, P., Falchi, M., Pirastu, M. Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate. Am. J. Hum. Genet. 72: 1479-1491, 2003. [PubMed: 12740763] [Full Text: https://doi.org/10.1086/375628]
Ombra, M. N., Forabosco, P., Casula, S., Angius, A., Maestrale, G., Petretto, E., Casu, G., Colussi, G., Usai, E., Melis, P., Pirastu, M. Identification of a new candidate locus for uric acid nephrolithiasis. Am. J. Hum. Genet. 68: 1119-1129, 2001. [PubMed: 11309680] [Full Text: https://doi.org/10.1086/320105]