title: Clinical and molecular characterization of maturity onset-diabetes of the young caused by hepatocyte nuclear factor-4 alpha mutation: red flags for prediction of the diagnosis.
abstract: OBJECTIVE
  The prevalence of maturity-onset diabetes of the young (MODY) in Saudi population remains unknown, and data on molecular etiology of this condition is limited. Therefore, the present study was undertaken to elucidate clinical and molecular characteristics of a Saudi family with MODY 1.
  
  
  METHODS
  This is a case series study conducted at Saad Specialist Hospital in Alkhobar, Saudi Arabia.
  
  
  METHODS
  A 12-year-old female presented to us with symptoms suggestive of diabetes. Investigations revealed hyperglycemia, glycosuria, and ketonuria without acidosis. Pancreatic antibodies were negative. She responded well to subcutaneous insulin. Her family history revealed that 2 of her siblings were diagnosed with type 1 diabetes (T1DM), while her father and mother had type 2 diabetes (T2DM). In view of this strong family history, the possibility of monogenic diabetes was raised, and the 2 genes consistent with this phenotype, hepatocyte nuclear factor-1 alpha (HNF1a) and hepatocyte nuclear factor-4 alpha (HNF4a), were studied. Accordingly, genomic DNA was isolated from peripheral blood lymphocytes of the 8 members of this family, polymerase chain reaction was carried out, and sequencing of the whole HNF4a and HNF1a genes was done.
  
  
  RESULTS
  DNA study of the proband revealed a heterozygous substitution in intron 1 (IVS1b C > T-5)(c.50-5C > T) of the HNF1a gene. This mutation was identified in other 5 members of the family.
  
  
  CONCLUSIONS
  This study alerts physicians to suspect MODY in patients who have a strongly positive family history of diabetes over a few generations with negative pancreatic antibodies and absence of ketoacidosis and obesity.
authors.affiliation: Sarar Mohamed, Department of Pediatrics,, College of Medicine,, King Saud University,, PO Box 2925, Riyadh 11461,, Saudi Arabia, T: +966541235272, F: +966114691512, sararmohamed@hotmail.com.
authors.forename: Sarar
authors.initials: S
authors.lastname: Mohamed
authors.forename: Susan
authors.initials: S
authors.lastname: Elkholy
authors.forename: Ebtessam
authors.initials: E
authors.lastname: El-Meleagy
authors.forename: Khaled
authors.initials: K
authors.lastname: Abu-Amero
authors.forename: Ali M
authors.initials: AM
authors.lastname: Hellani
mesh_terms: D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005192:Family Health; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D009154:Mutation; D012529:Saudi Arabia
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D007004:Hypoglycemic Agents; D007328:Insulin