Clinical and genetic analysis in a Chinese cohort of children and adolescents with diabetes/persistent hyperglycemia.

Publisher: Asian Association for the Study of Diabetes and Blackwell Pub. Asia Country of Publication: Japan NLM ID: 101520702 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2040-1124 (Electronic) Linking ISSN: 20401116 NLM ISO Abbreviation: J Diabetes Investig Subsets: MEDLINE

Original Publication: Tokyo : Asian Association for the Study of Diabetes and Blackwell Pub. Asia

Mutation*; Asian People/*genetics ; Biomarkers/*analysis ; Diabetes Mellitus, Type 2/*epidemiology ; Genetic Testing/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Hyperglycemia/*epidemiology; Adolescent ; Blood Glucose/analysis ; Child ; Child, Preschool ; China/epidemiology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Female ; Follow-Up Studies ; Glycated Hemoglobin/analysis ; Humans ; Hyperglycemia/genetics ; Hyperglycemia/pathology ; Infant ; Male ; Prognosis

Aims/introduction: To investigate the genetic etiology and evaluate the diagnostic application of next-generation sequencing for diabetes/persistent hyperglycemia in children and adolescents.
Materials and Methods: Patients with diabetes/persistent hyperglycemia, presenting with at least one other clinical manifestation (other than diabetes) or with a family history of diabetes, were recruited. The clinical and laboratory characteristics of the patients were recorded. Next-generation sequencing was carried out, and candidate variants were verified by Sanger sequencing. Variant pathogenicity was further evaluated according to the American College of Medical Genetics and Genomics guidelines.
Results: This study included 101 potential probands, 36 of whom were identified as positive by genetic testing. A further 51.2 and 20.9% of variants were determined to be pathogenic or likely pathogenic, respectively. Variants associated with the disease were primarily identified in 21 genes and three regions of copy number variants. Among the 39 variants in 21 genes, 61.5% (24/39) were novel. The genetic diagnosis of 23 patients was confirmed based on genetic evidence and associated clinical manifestations. We reported GCK variants (21.7%, 5/23) as the most common etiology in our cohort. Different clinical manifestations were observed in one family with WFS1 variants.
Conclusions: Our findings support the use of next-generation sequencing as a standard method in patients with diabetes/persistent hyperglycemia and provide insights into the etiologies of these conditions.
(© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Genet Med. 2018 Sep;20(9):1045-1053. (PMID: 29095814)
Pediatr Diabetes. 2016 Aug;17(5):360-7. (PMID: 26059258)
Diabetes. 2019 Jul;68(7):1523-1527. (PMID: 30962219)
J Med Genet. 2004 Jun;41(6):433-9. (PMID: 15173228)
Hum Mutat. 2018 Nov;39(11):1517-1524. (PMID: 30192042)
Am J Med Genet C Semin Med Genet. 2007 Aug 15;145C(3):248-60. (PMID: 17640042)
Genet Med. 2015 May;17(5):405-24. (PMID: 25741868)
Diabetes. 2013 Nov;62(11):3943-50. (PMID: 23903355)
J Clin Endocrinol Metab. 2019 Apr 12;:. (PMID: 30977832)
Diabetes Res Clin Pract. 2019 May;151:231-236. (PMID: 31063852)
J Bone Miner Res. 2016 Apr;31(4):882-9. (PMID: 26643732)
Pediatr Diabetes. 2018 Feb;19(1):53-58. (PMID: 28436179)
Lancet. 1995 Mar 11;345(8950):648. (PMID: 7898196)
Nat Genet. 2009 Jun;41(6):703-7. (PMID: 19430480)
J Med Genet. 2020 Feb;57(2):121-123. (PMID: 31363008)
Diabetes Res Clin Pract. 2015 Mar;107(3):e15-8. (PMID: 25649912)
Exp Diabetes Res. 2011;2011:498460. (PMID: 21754918)
Clin Genet. 2015 May;87(5):440-7. (PMID: 24735133)
Mol Genet Genomic Med. 2019 Jan;7(1):e00513. (PMID: 30565893)
J Pediatr Endocrinol Metab. 2019 Jul 26;32(7):759-765. (PMID: 31216263)
Exp Clin Endocrinol Diabetes. 2017 Sep;125(8):563-570. (PMID: 28750427)
Eur J Med Genet. 2017 Nov;60(11):583-588. (PMID: 28811188)
Diabetes. 2005 Dec;54 Suppl 2:S125-36. (PMID: 16306330)
J Diabetes Investig. 2019 Jul;10(4):963-971. (PMID: 30592380)
Genet Med. 2018 Dec;20(12):1687-1688. (PMID: 29543229)
Hum Mutat. 2017 Jul;38(7):764-777. (PMID: 28432734)
J Diabetes Investig. 2019 Jul;10(4):947-950. (PMID: 30414308)
Mol Genet Metab. 2014 Dec;113(4):315-320. (PMID: 25306193)
PLoS Comput Biol. 2016 Apr 21;12(4):e1004873. (PMID: 27100738)
Genet Med. 2011 Jul;13(7):680-5. (PMID: 21681106)
Diabetologia. 2010 Dec;53(12):2504-8. (PMID: 20499044)
Diabetes Care. 2014;37(5):1230-6. (PMID: 24550216)
Am J Med Genet A. 2015 Jan;167A(1):185-9. (PMID: 25402011)
PLoS One. 2015 Nov 23;10(11):e0143373. (PMID: 26599467)
Diabetologia. 2017 Apr;60(4):625-635. (PMID: 27913849)
Genet Med. 2015 Jun;17(6):444-51. (PMID: 25232854)
J Diabetes Investig. 2021 Jan;12(1):48-62. (PMID: 32531870)
Acta Diabetol. 2016 Oct;53(5):703-8. (PMID: 27106716)
Diabetes. 2020 Jan;69(1):121-126. (PMID: 31658956)
Genet Med. 2016 Nov;18(11):1090-1096. (PMID: 26938784)

8190072 National Natural Science Foundation of China; 81370930 National Natural Science Foundation of China; PEGRF201506011 Shanghai Children's Medical Center Research Project; YG2016QN39 Cross Research Fund for Medical Engineering of Shanghai Jiao Tong University; 2016YFC1305203 National Science and Technology Commission

Keywords: Diabetes mellitus; Genetic etiology; Next-generation sequencing

0 (Biomarkers)
0 (Blood Glucose)
0 (Glycated Hemoglobin A)
0 (hemoglobin A1c protein, human)

Date Created: 20200613 Date Completed: 20211004 Latest Revision: 20221207

20221213

PMC7779271

10.1111/jdi.13322

32531870