title: Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5.
abstract: 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 dominant TCF2 anomalies.
  
  
  METHODS
  MEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germline TCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification (hypomethylation and hypermethylation), loci associated with cancer risk, and somatic TCF2 anomalies were all excluded.
  
  
  METHODS
  After searching the literature, 50 articles were selected.
  
  
  RESULTS
  The detection rate of TCF2 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 with TCF2 anomalies. Analysis of phenotypes of TCF2 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.
  
  
  CONCLUSIONS
  These valuable features of TCF2 anomalies that previously did not receive sufficient attention should not be neglected.
authors.affiliation: Division of Nephrology, Kidney Institute and Key Lab of Chinese People's Liberation Army, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Yi-Zhi
authors.initials: YZ
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.forename: Xue-Zhi
authors.initials: XZ
authors.lastname: Zhao
authors.forename: Ying-Zhang
authors.initials: YZ
authors.lastname: Chen
authors.forename: Craig L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Xi-Shan
authors.initials: XS
authors.lastname: Xiong
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Mei
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Shi
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Chen
mesh_terms: D002493:Central Nervous System Diseases / Q000378:metabolism; D003743:Dental Enamel / Q000002:abnormalities / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism*; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000378:metabolism
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta