Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5

摘要

Objective There is a paucity of published works that systematically evaluate gene anomalies or clinical features of patients with renal cysts and diabetes syndrome （RCAD）/maturity onset diabetes of the young type 5 （MODY5）. The purpose of this review was to systematically assess the detection rate, genetic and phenotypic implications of heterozygous autosomal dominantTCF2 anomalies.Data sources MEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germlineTCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification （hypomethylation and hypermethylation）, loci associated with cancer risk, and somaticTCF2 anomalies were all excluded. Study selection After searching the literature, 50 articles were selected.Results The detection rate ofTCF2 anomalies was 9.7% and varied considerably among MODY （1.4%）, renal structure anomalies （RSA） （21.4%） and RSA with MODY （41.2%） subgroups. Mutations were strikingly located within the DNA binding domain and varied among exons of the DNA binding domain: exons 2 and 4 were the hottest spots, while mutations were sporadically distributed in exon 3. The consistent phenotypes were RSA （89.6%） and diabetes mellitus （DM） （45.0%）. However, the concurrence of RSA and DM was relatively low （27.5%）, which hinders the optimal performance of genetic testing and obtainment of timely diagnosis. Other organ involvements were complementary and necessary for the early identification of patients withTCF2 anomalies. Analysis of phenotypes ofTCF2 point mutations showed significant differences in the detection rates of RSA, impaired renal function （IRF） and DM according to mutation type but not mutation location.Conclusion These valuable features ofTCF2 anomalies that previously did not receive sufficient attention should not be neglected.