title: The glucokinase mutation p.T206P is common among MODY patients of Jewish Ashkenazi descent.
abstract: BACKGROUND
  Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance; a primary defect in insulin secretion with non-ketotic hyperglycemia, age of onset under 25 yr; and lack of autoantibodies. Heterozygous mutations in glucokinase (GCK) are associated with mild fasting hyperglycemia and gestational diabetes mellitus while homozygous or compound heterozygous GCK mutations result in permanent neonatal diabetes mellitus. Given that both the Israeli-Arabic and the various Israeli-Jewish communities tend to maintain ethnic seclusion, we speculated that it would be possible to identify a relatively narrow spectrum of mutations in the Israeli population.
  
  
  OBJECTIVE
  To characterize the genetic basis of GCK-MODY in the different ethnic groups of the Israeli population.
  
  
  METHODS
  Patients with clinically identified GCK-MODY and their first degree family members.
  
  
  METHODS
  Molecular analysis of GCK was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and sequencing. Bioinformatic model was preformed using the NEST program.
  
  
  RESULTS
  Mutations in GCK were identified in 25 families and were all family-specific, except c.616A>C. p.T206P. This mutation was identified in six unrelated families, all patients from a Jewish-Ashkenazi descent, thus indicating an ethno-genetic correlation. A simple, fast, and relatively cheap DGGE/restriction-digestion assay was developed.
  
  
  CONCLUSIONS
  The high incidence of the mutant allele in GCK-MODY patients of Jewish-Ashkenazi descent suggests a founder effect. We propose that clinically identified GCK-MODY patients of Jewish-Ashkenazi origin be first tested for this mutation.
authors: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors: Yael
authors: Y
authors: Gozlan
authors: Ariel
authors: A
authors: Tenenbaum
authors: Shlomit
authors: S
authors: Shalitin
authors: Yael
authors: Y
authors: Lebenthal
authors: Tal
authors: T
authors: Oron
authors: Ohad
authors: O
authors: Cohen
authors: Moshe
authors: M
authors: Phillip
authors: Galia
authors: G
authors: Gat-Yablonski
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005190:Family; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005941:Glucokinase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007223:Infant; D007557:Israel / Q000208:ethnology; D007585:Jews / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense / Q000502:physiology; D055815:Young Adult
chemical_list: D005941:Glucokinase