title: Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia.
abstract: BACKGROUND
  Permanent neonatal diabetes mellitus (PNDM) in European population has an incidence of at least 1 in 260 000 live births and is most commonly due to mutations in KCNJ11 and ABCC8. However, data on this condition in other populations are limited.
  
  
  OBJECTIVE
  To define the incidence, genetic aetiology, and clinical phenotype of PNDM in Al-Madinah region, northwest Saudi Arabia.
  
  
  METHODS
  Patients with PNDM diagnosed between 2001 and 2010 were identified and clinically phenotyped. Sequencing of KCNJ11, ABCC8, and INS were performed initially on all subjects, and EIF2AK3, GLIS3, SLC2A2, SLC19A2, GCK, IPF1, and NEUROD1 genes were sequenced according to the clinical phenotype.
  
  
  RESULTS
  In total, 17 patients from 11 consanguineous families were diagnosed with PNDM and the incidence was 1 in 21 196 live births. Six different mutations in four genes were identified, of which two GLIS3 and one SLC2A2 were novel and no patient had KCNJ11, ABCC8, or INS mutations. Fourteen (82.4%) patients had identifiable genetic aetiology and their PNDM was part of known autosomal-recessive syndromes including Wolcott Rallison (41.1%), neonatal diabetes and hypothyroidism (29.4%), Fanconi-Bickel (5.8%), and thiamine-responsive megaloblastic anaemia (5.8%). Two patients with isolated PNDM and one with intermediate developmental delay, epilepsy and neonatal diabetes had no identifiable cause.
  
  
  CONCLUSIONS
  Al-Madinah region has the highest reported incidence of PNDM worldwide. In this region with high consanguinity, PNDM has different genetic aetiology and in the majority of cases presents as a part of rare familial autosomal-recessive syndrome rather than in isolation.
authors: Endocrine and Diabetes Unit, Maternity and Children Hospital, Al-Madinah, Kingdom of Saudi Arabia. amhabeb@hotmail.com
authors: Abdelhadi M
authors: AM
authors: Habeb
authors: Mohamed S F
authors: MS
authors: Al-Magamsi
authors: Ihsan M
authors: IM
authors: Eid
authors: Mohamed I
authors: MI
authors: Ali
authors: Andrew T
authors: AT
authors: Hattersley
authors: Khalid
authors: K
authors: Hussain
authors: Sian
authors: S
authors: Ellard
mesh_terms: D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D010641:Phenotype; D012529:Saudi Arabia / Q000453:epidemiology