Journal of pediatric endocrinology & metabolism : JPEM · 2018
Genetic mutations associated with neonatal diabetes mellitus in Omani patients.
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Al Senani Aisha, Hamza Nishath, Al Azkawi Hanan, Al Kharusi Manal, Al Sukaiti Nashat, Al Badi Maryam, Al Yahyai Moza, Johnson Matthew, De Franco Elisa, Flanagan Sarah, Hattersley Andrew, Ellard Sian, Mula-Abed Waad-Allah
Аннотация
BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where diabetes is diagnosed in the first 6 months of life. However, Oman has a relatively high incidence of NDM.
METHODS: In this study, we investigated the genetic etiologies underlying NDM and their prevalence in Oman. We collected a cohort of 24 NDM patients, with and without genetic diagnosis, referred to our center from 2007 to 2015. All patients without a genetic diagnosis were tested for mutations in 23 NDM-associated genes using a custom-targeted next-generation sequencing (NGS) panel and methylation analysis of the 6q24 locus.
RESULTS: A genetic abnormality was detected in 15/24 (62.5%) of our Omani NDM patients. We report the detection of 6q24 methylation abnormalities and KCNJ11 mutations for the first time in Omani NDM patients. Unlike Western populations where NDM is predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to homozygous GCK gene mutations were most prevalent in Oman, having been observed in seven out of 15 NDM patients in whom we established the genetic etiology. This reflects the high degree of consanguinity which makes recessive conditions more likely.
CONCLUSIONS: The results of this study are likely to impact any future strategy to introduce genetic testing for NDM disorders within the national healthcare system in Oman.
METHODS: In this study, we investigated the genetic etiologies underlying NDM and their prevalence in Oman. We collected a cohort of 24 NDM patients, with and without genetic diagnosis, referred to our center from 2007 to 2015. All patients without a genetic diagnosis were tested for mutations in 23 NDM-associated genes using a custom-targeted next-generation sequencing (NGS) panel and methylation analysis of the 6q24 locus.
RESULTS: A genetic abnormality was detected in 15/24 (62.5%) of our Omani NDM patients. We report the detection of 6q24 methylation abnormalities and KCNJ11 mutations for the first time in Omani NDM patients. Unlike Western populations where NDM is predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to homozygous GCK gene mutations were most prevalent in Oman, having been observed in seven out of 15 NDM patients in whom we established the genetic etiology. This reflects the high degree of consanguinity which makes recessive conditions more likely.
CONCLUSIONS: The results of this study are likely to impact any future strategy to introduce genetic testing for NDM disorders within the national healthcare system in Oman.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAmino Acid SubstitutionChromosomes, Human, Pair 6Cohort StudiesConsanguinityDNA MethylationDNA Mutational AnalysisDiabetes MellitusExonsFemaleGerminal Center KinasesGlucose Transporter Type 2HumansInfantInfant, NewbornInterleukin-2 Receptor alpha SubunitMaleMutationOmanPedigreePotassium Channels, Inwardly RectifyingPrevalenceProtein Serine-Threonine KinasesKcnj11 ChannelImprinting Disorders