Objective Mutations in the KCNJ11 and ABCC8 genes that encode the pancreatic KATP 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.
Design Retrospective observational study.
Setting International genetics centre.
Patients Arab and British subjects with PNDM who were referred for genetic testing over the same period.
Intervention Comparison of genotypes and phenotypes between the two cohorts.
Main outcome measures 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 KATP 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.
Conclusion 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.
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Contributors AMH:conception and design of the study, data analysis and interpretation, drafting of the article and final approval of the manuscript; SEF, AD, ATH, KH and SE: conception and design of the study, analysis and interpretation of data, and revision and final approval of the manuscript; IAA, HA, AB and AM: conception and design of the study, revision of data analysis and final approval of the manuscript.
Funding This work was funded by the Wellcome Trust (grant 067463/Z/2/Z). ATH was a Wellcome Trust Research Leave Fellow. SEF is the Sir Graham WilkINS, PenINSula Medical School Research Fellow and SE is employed as a core member of staff within the NIHR funded PenINSula Clinical Research Facility.
Ethics approval The study was approved by the South West Ethics Committee (UK).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.