title: Four novel mutations, including the first gross deletion in TCF1, identified in HNF-4alpha, GCK and TCF1 in patients with MODY in Israel.
abstract: Maturity onset diabetes of the young (MODY) is characterized by a primary defect in insulin secretion with non-ketotic hyperglycemia, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of autoantibodies. The aim of this study was to characterize the genetic basis of MODY in different ethnic groups in the Israeli population. Fifty-nine unrelated Israeli patients with MODY were assessed for mutations in the three common MODY genes: hepatocyte nuclear factor (HNF)-4alpha, glucokinase (GCK), and transcription factor 1 (TCF1). Overall, 11 mutations in 12 unrelated families were found (20.3% of patients), for a relative frequency of 1.7% for MODY1, 8.5% for MODY2, and 10.1% for MODY3. Four mutations were novel, including the first gross deletion ever described in the TCF1 gene. The low overall mutation frequency found here may suggest the involvement of other, yet unidentified, genes in the etiology of MODY in Israel.
authors.affiliation: Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Stern
authors.forename: C
authors.initials: C
authors.lastname: Strihan
authors.forename: O
authors.initials: O
authors.lastname: Potievsky
authors.forename: R
authors.initials: R
authors.lastname: Nimri
authors.forename: S
authors.initials: S
authors.lastname: Shalitin
authors.forename: O
authors.initials: O
authors.lastname: Cohen
authors.forename: N
authors.initials: N
authors.lastname: Shehadeh
authors.forename: N
authors.initials: N
authors.lastname: Weintrob
authors.forename: M
authors.initials: M
authors.lastname: Phillip
authors.forename: G
authors.initials: G
authors.lastname: Gat-Yablonski
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D005941:Glucokinase / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007557:Israel; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D005941:Glucokinase