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Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations

BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual inciden...

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Autores principales: Demirbilek, Huseyin, Arya, Ved Bhushan, Ozbek, Mehmet Nuri, Houghton, Jayne A L, Baran, Riza Taner, Akar, Melek, Tekes, Selahattin, Tuzun, Heybet, Mackay, Deborah J, Flanagan, Sarah E, Hattersley, Andrew T, Ellard, Sian, Hussain, Khalid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411707/
https://www.ncbi.nlm.nih.gov/pubmed/25755231
http://dx.doi.org/10.1530/EJE-14-0852
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author Demirbilek, Huseyin
Arya, Ved Bhushan
Ozbek, Mehmet Nuri
Houghton, Jayne A L
Baran, Riza Taner
Akar, Melek
Tekes, Selahattin
Tuzun, Heybet
Mackay, Deborah J
Flanagan, Sarah E
Hattersley, Andrew T
Ellard, Sian
Hussain, Khalid
author_facet Demirbilek, Huseyin
Arya, Ved Bhushan
Ozbek, Mehmet Nuri
Houghton, Jayne A L
Baran, Riza Taner
Akar, Melek
Tekes, Selahattin
Tuzun, Heybet
Mackay, Deborah J
Flanagan, Sarah E
Hattersley, Andrew T
Ellard, Sian
Hussain, Khalid
author_sort Demirbilek, Huseyin
collection PubMed
description BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.
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spelling pubmed-44117072015-06-01 Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations Demirbilek, Huseyin Arya, Ved Bhushan Ozbek, Mehmet Nuri Houghton, Jayne A L Baran, Riza Taner Akar, Melek Tekes, Selahattin Tuzun, Heybet Mackay, Deborah J Flanagan, Sarah E Hattersley, Andrew T Ellard, Sian Hussain, Khalid Eur J Endocrinol Clinical Study BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort. Bioscientifica Ltd 2015-06 /pmc/articles/PMC4411707/ /pubmed/25755231 http://dx.doi.org/10.1530/EJE-14-0852 Text en © 2015 The authors http://creativecommons.org/licenses/by/3.0/deed.en_GB This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/deed.en_GB)
spellingShingle Clinical Study
Demirbilek, Huseyin
Arya, Ved Bhushan
Ozbek, Mehmet Nuri
Houghton, Jayne A L
Baran, Riza Taner
Akar, Melek
Tekes, Selahattin
Tuzun, Heybet
Mackay, Deborah J
Flanagan, Sarah E
Hattersley, Andrew T
Ellard, Sian
Hussain, Khalid
Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations
title Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations
title_full Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations
title_fullStr Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations
title_full_unstemmed Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations
title_short Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-K(ATP) channel mutations
title_sort clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the south-eastern region of turkey: predominance of non-k(atp) channel mutations
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411707/
https://www.ncbi.nlm.nih.gov/pubmed/25755231
http://dx.doi.org/10.1530/EJE-14-0852
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