Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age

Background. Maturity-onset diabetes of the young (MODY) is commonly misdiagnosed as type 1 or type 2 diabetes. Common reasons for misdiagnosis are related to limitations in genetic testing. A precise molecular diagnosis is essential for the optimal treatment of patients and allows for early diagnosi...

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Autores principales:	Rumi Katashima, Mari Matsumoto, Yuka Watanabe, Maki Moritani, Ichiro Yokota
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/03829d726785418c91cc487afa340338
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spelling	oai:doaj.org-article:03829d726785418c91cc487afa3403382021-11-08T02:36:34ZIdentification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age2314-675310.1155/2021/7216339https://doaj.org/article/03829d726785418c91cc487afa3403382021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/7216339https://doaj.org/toc/2314-6753Background. Maturity-onset diabetes of the young (MODY) is commonly misdiagnosed as type 1 or type 2 diabetes. Common reasons for misdiagnosis are related to limitations in genetic testing. A precise molecular diagnosis is essential for the optimal treatment of patients and allows for early diagnosis of their asymptomatic family members. Objective. The aim of this study was to identify rare monogenic variants of common MODY genes in Japanese pediatric patients. Methods. We investigated 45 Japanese pediatric patients based on the following clinical criteria: development of diabetes before 17 years of age, a family history of diabetes, testing negative for glutamate decarboxylase-65 (GAD 65) antibodies and insulinoma-2-associated autoantibodies (IA-2A), no significant obesity, and evidence of endogenous insulin production. Genetic screening for MODY1 (HNF4α), MODY2 (GCK), MODY3 (HNF1α), and MODY5 (HNF1β) was performed by direct sequencing followed by multiplex ligation amplification assays. Results. We identified 22 missense variants (3 novel variants) in 27 patients (60.0%) in the GCK, HNF4α, and HNF1α genes. We also detected a whole exon deletion in the HNF1β gene and an exon 5–6 aberration in the GCK gene, each in one proband (4.4%). There were a total of 29 variations (64.4%), giving a relative frequency of 53.3% (24/45) for GCK, 2.2% (1/45) for HNF4α, 6.7% (3/45) for HNF1α, and 2.2% (1/45) for HNF1β genes. Conclusions. Clinicians should consider collecting and assessing detailed clinical information, especially regarding GCK gene variants, in young antibody-negative patients with diabetes. Correct molecular diagnosis of MODY better predicts the clinical course of diabetes and facilitates individualized management.Rumi KatashimaMari MatsumotoYuka WatanabeMaki MoritaniIchiro YokotaHindawi LimitedarticleDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENJournal of Diabetes Research, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Diseases of the endocrine glands. Clinical endocrinology RC648-665 Rumi Katashima Mari Matsumoto Yuka Watanabe Maki Moritani Ichiro Yokota Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age
description	Background. Maturity-onset diabetes of the young (MODY) is commonly misdiagnosed as type 1 or type 2 diabetes. Common reasons for misdiagnosis are related to limitations in genetic testing. A precise molecular diagnosis is essential for the optimal treatment of patients and allows for early diagnosis of their asymptomatic family members. Objective. The aim of this study was to identify rare monogenic variants of common MODY genes in Japanese pediatric patients. Methods. We investigated 45 Japanese pediatric patients based on the following clinical criteria: development of diabetes before 17 years of age, a family history of diabetes, testing negative for glutamate decarboxylase-65 (GAD 65) antibodies and insulinoma-2-associated autoantibodies (IA-2A), no significant obesity, and evidence of endogenous insulin production. Genetic screening for MODY1 (HNF4α), MODY2 (GCK), MODY3 (HNF1α), and MODY5 (HNF1β) was performed by direct sequencing followed by multiplex ligation amplification assays. Results. We identified 22 missense variants (3 novel variants) in 27 patients (60.0%) in the GCK, HNF4α, and HNF1α genes. We also detected a whole exon deletion in the HNF1β gene and an exon 5–6 aberration in the GCK gene, each in one proband (4.4%). There were a total of 29 variations (64.4%), giving a relative frequency of 53.3% (24/45) for GCK, 2.2% (1/45) for HNF4α, 6.7% (3/45) for HNF1α, and 2.2% (1/45) for HNF1β genes. Conclusions. Clinicians should consider collecting and assessing detailed clinical information, especially regarding GCK gene variants, in young antibody-negative patients with diabetes. Correct molecular diagnosis of MODY better predicts the clinical course of diabetes and facilitates individualized management.
format	article
author	Rumi Katashima Mari Matsumoto Yuka Watanabe Maki Moritani Ichiro Yokota
author_facet	Rumi Katashima Mari Matsumoto Yuka Watanabe Maki Moritani Ichiro Yokota
author_sort	Rumi Katashima
title	Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age
title_short	Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age
title_full	Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age
title_fullStr	Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age
title_full_unstemmed	Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age
title_sort	identification of novel gck and hnf4α gene variants in japanese pediatric patients with onset of diabetes before 17 years of age
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/03829d726785418c91cc487afa340338
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Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age

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