The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar

Sara Al-Khawaga, Idris Mohammed, Saras Saraswathi, Basma Haris, Reem Hasnah, Amira Saeed, Hakeem Almabrazi, Najeeb Syed, Puthen V. Jithesh, Ahmed El Awwa, Amal Khalifa, Fawziya AlKhalaf, Goran Petrovski, Essam Mohamed, Khalid Hussain

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere753
JournalMolecular Genetics and Genomic Medicine
DOIs
Publication statusPublished - 1 Jan 2019

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Qatar
Diabetes Mellitus
Live Birth
Mutation
Pancreas
Incidence
Transcription Factors
Insulin-Secreting Cells
Genomics
Marriage
Population
Genes
Cell Survival
Genome
Insulin

Keywords

  • Fanconi–Bickel Syndrome (FBS)
  • GCK
  • HNF1B
  • INS
  • pancreatic agenesis
  • Permanent neonatal diabetes (PNDM)
  • PTF1A
  • Whole Genome Sequencing (WGS)
  • Wolcott–Rallison Syndrome (WRS)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar. / Al-Khawaga, Sara; Mohammed, Idris; Saraswathi, Saras; Haris, Basma; Hasnah, Reem; Saeed, Amira; Almabrazi, Hakeem; Syed, Najeeb; Jithesh, Puthen V.; El Awwa, Ahmed; Khalifa, Amal; AlKhalaf, Fawziya; Petrovski, Goran; Mohamed, Essam; Hussain, Khalid.

In: Molecular Genetics and Genomic Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Al-Khawaga, S, Mohammed, I, Saraswathi, S, Haris, B, Hasnah, R, Saeed, A, Almabrazi, H, Syed, N, Jithesh, PV, El Awwa, A, Khalifa, A, AlKhalaf, F, Petrovski, G, Mohamed, E & Hussain, K 2019, 'The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar', Molecular Genetics and Genomic Medicine. https://doi.org/10.1002/mgg3.753
Al-Khawaga, Sara ; Mohammed, Idris ; Saraswathi, Saras ; Haris, Basma ; Hasnah, Reem ; Saeed, Amira ; Almabrazi, Hakeem ; Syed, Najeeb ; Jithesh, Puthen V. ; El Awwa, Ahmed ; Khalifa, Amal ; AlKhalaf, Fawziya ; Petrovski, Goran ; Mohamed, Essam ; Hussain, Khalid. / The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar. In: Molecular Genetics and Genomic Medicine. 2019.
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abstract = "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.",
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AU - Mohammed, Idris

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AU - Haris, Basma

AU - Hasnah, Reem

AU - Saeed, Amira

AU - Almabrazi, Hakeem

AU - Syed, Najeeb

AU - Jithesh, Puthen V.

AU - El Awwa, Ahmed

AU - Khalifa, Amal

AU - AlKhalaf, Fawziya

AU - Petrovski, Goran

AU - Mohamed, Essam

AU - Hussain, Khalid

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N2 - 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.

AB - 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.

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KW - Whole Genome Sequencing (WGS)

KW - Wolcott–Rallison Syndrome (WRS)

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