title: Permanent neonatal diabetes: different aetiology in Arabs compared to Europeans.
abstract: OBJECTIVE
  Mutations in the KCNJ11 and ABCC8 genes that encode the pancreatic K(ATP) channel are the commonest cause of permanent neonatal diabetes mellitus (PNDM). The authors aimed to define the genetic causes of PNDM in a large cohort of Arab patients and compare them with a British cohort tested in the same laboratory.
  
  
  METHODS
  Retrospective observational study.
  
  
  METHODS
  International genetics centre.
  
  
  METHODS
  Arab and British subjects with PNDM who were referred for genetic testing over the same period.
  
  
  METHODS
  Comparison of genotypes and phenotypes between the two cohorts.
  
  
  METHODS
  The aetiology and phenotype of PNDM in an Arab compared to a British cohort.
  
  
  RESULTS
  88 Arab and 77 British probands were referred between 2006 and 2011, inclusive. Consanguinity was higher among Arabs (63.6% vs 10.4%) and a higher percentage had a genetic diagnosis compared to the British cohort (63.6% vs 41.6%). Recessive EIF2AK3 gene mutations were the commonest cause of PNDM in the Arab cohort (22.7%) followed by INS (12.5%), and KCNJ11 and GCK (5.7% each), whereas K(ATP) channel mutations were the commonest cause (29.9%) in the British cohort. In 37.5% of Arab patients PNDM was part of a genetic syndrome compared to 7.8% of the British cohort.
  
  
  CONCLUSIONS
  PNDM in the Arab population has a different genetic spectrum compared to British patients where KATP channel mutations are the commonest cause, similar to other European populations. In Arabs, PNDM is more likely to be part of a recessively inherited syndrome, possibly due to the higher rate of consanguinity.
authors.affiliation: Department of Paediatrics, Maternity and Children's Hospital, PO Box 20873, Al-Madinah 41465, Saudi Arabia. amhabeb@hotmail.com
authors.forename: Abdelhadi M
authors.initials: AM
authors.lastname: Habeb
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Asma
authors.initials: A
authors.lastname: Deeb
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Alwan
authors.forename: Hussain
authors.initials: H
authors.lastname: Alawneh
authors.forename: Angham A L
authors.initials: AA
authors.lastname: Balafrej
authors.forename: Angam
authors.initials: A
authors.lastname: Mutair
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D018912:Arabs / Q000208:ethnology / Q000235:genetics*; D003241:Consanguinity; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D000081410:Germinal Center Kinases; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000208:ethnology / Q000235:genetics*; D054086:KATP Channels / Q000235:genetics; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012189:Retrospective Studies; D044465:White People / Q000208:ethnology / Q000235:genetics*; D019892:eIF-2 Kinase / Q000235:genetics; D000099161:Kcnj11 Channel
chemical_list: D000081410:Germinal Center Kinases; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D000099161:Kcnj11 Channel; C460640:EIF2AK3 protein, human