Search

Aims/Introduction To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar. Materials and methods All patients (aged 0–18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated. Results Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000. Conclusions This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non‐Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus., This is the first comprehensive, prospective study from the Middle East North Africa region to systematically study the causes of diabetes in every child in the State of Qatar. The State of Qatar has the fourth highest incidence of type 1 diabetes in the world. The incidence of type 2 diabetes is much higher in Qatar than in Western countries. Both type 1 and type 2 diabetes are more common in the Qatari population than the non‐Qatari population. Mutations in GCK were the most common cause of maturity onset diabetes of the young, and mutations in the PTF1A and INS genes were the most common cause of neonatal diabetes in this population.

We report a pleiotropic disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in two kindreds with recurrent infections in different organs. One patient had recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement and the other two experienced recurrent respiratory infections. Loss of iRHOM2, a rhomboid superfamily member that regulates the ADAM17 metalloproteinase, caused defective ADAM17-dependent cleavage and release of cytokines, including tumor-necrosis factor and amphiregulin. To understand the diverse clinical phenotypes, we challenged Rhbdf2

Background Neonatal diabetes mellitus (NDM) is a rare condition that occurs within the first six months of life. Permanent NDM (PNDM) is caused by mutations in specific genes that are known for their expression at early and/or late stages of pancreatic beta‐ cell development, and are either involved in beta‐cell survival, insulin processing, regulation, and release. The native population in Qatar continues to practice consanguineous marriages that lead to a high level of homozygosity. To our knowledge, there is no previous report on the genomics of NDM among the Qatari population. The aims of the current study are to identify patients with NDM diagnosed between 2001 and 2016, and examine their clinical and genetic characteristics. Methods To calculate the incidence of PNDM, all patients with PNDM diagnosed between 2001 and 2016 were compared to the total number of live births over the 16‐year‐period. Whole Genome Sequencing (WGS) was used to investigate the genetic etiology in the PNDM cohort. Results PNDM was diagnosed in nine (n = 9) patients with an estimated incidence rate of 1:22,938 live births among the indigenous Qatari. Seven different mutations in six genes (PTF1A, GCK, SLC2A2, EIF2AK3, INS, and HNF1B) were identified. In the majority of cases, the genetic etiology was part of a previously identified autosomal recessive disorder. Two novel de novo mutations were identified in INS and HNF1B. Conclusion Qatar has the second highest reported incidence of PNDM worldwide. A majority of PNDM cases present as rare familial autosomal recessive disorders. Pancreas associated transcription factor 1a (PTF1A) enhancer deletions are the most common cause of PNDM in Qatar, with only a few previous cases reported in the literature.