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Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia
Author(s) -
Habeb Abdelhadi M,
AlMagamsi Mohamed SF,
Eid Ihsan M,
Ali Mohamed I,
Hattersley Andrew T,
Hussain Khalid,
Ellard Sian
Publication year - 2012
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/j.1399-5448.2011.00828.x
Subject(s) - medicine , incidence (geometry) , diabetes mellitus , phenotype , pediatrics , genetics , endocrinology , gene , biology , physics , optics
Habeb AM, Al‐Magamsi MSF, Eid IM, Ali MI, Hattersley AT, Hussain K, Ellard S. Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia. 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.