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Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes

Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) is characterized by asymptomatic, non-progressive and fasting hyperglycemia, albeit not without phenotypic variability. We used next generation sequencing (NGS) to screen for 34 MODY genes in a non-obese person with familial young-onset dia...

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Autores principales: Thewjitcharoen, Yotsapon, Wanothayaroj, Ekgaluck, Krittiyawong, Sirinate, Nakasatien, Soontaree, Tsoi, Tsz Fung, Lim, Cadmon K. P., Chan, Juliana C. N., Himathongkam, Thep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498575/
https://www.ncbi.nlm.nih.gov/pubmed/34630320
http://dx.doi.org/10.3389/fendo.2021.690343
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author Thewjitcharoen, Yotsapon
Wanothayaroj, Ekgaluck
Krittiyawong, Sirinate
Nakasatien, Soontaree
Tsoi, Tsz Fung
Lim, Cadmon K. P.
Chan, Juliana C. N.
Himathongkam, Thep
author_facet Thewjitcharoen, Yotsapon
Wanothayaroj, Ekgaluck
Krittiyawong, Sirinate
Nakasatien, Soontaree
Tsoi, Tsz Fung
Lim, Cadmon K. P.
Chan, Juliana C. N.
Himathongkam, Thep
author_sort Thewjitcharoen, Yotsapon
collection PubMed
description Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) is characterized by asymptomatic, non-progressive and fasting hyperglycemia, albeit not without phenotypic variability. We used next generation sequencing (NGS) to screen for 34 MODY genes in a non-obese person with familial young-onset diabetes followed by screening in 24 family members within three generations with varying presentations of young-onset diabetes and sensorineural hearing loss. The index patient was found to carry a paternally-inherited heterozygous missense variant (c.716 A>G) of GCK in exon 7 with amino acid change (Q239R). This variant was associated with phenotypic heterogeneity ranging from normal glucose tolerance to diabetes with complications amongst the siblings which might be modified by obesity and chronic hepatitis B infection. Two paternally-inherited variants of SLC29A3 encoding a nucleoside transporter protein and Apo-A1 genes also co-segregated with glucose and lipid traits. Co-occurrence of diabetes and deafness in maternal aunts led to discovery of WFS1 (Wolfram syndrome type 1) as a cause of non-syndromic deafness in multiple members of the maternal pedigree. Our findings highlight the complex causes of familial young-onset diabetes and the need of a multidisciplinary approach to interpret the clinical relevance of discoveries made by NGS in this era of genomic medicine.
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spelling pubmed-84985752021-10-09 Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes Thewjitcharoen, Yotsapon Wanothayaroj, Ekgaluck Krittiyawong, Sirinate Nakasatien, Soontaree Tsoi, Tsz Fung Lim, Cadmon K. P. Chan, Juliana C. N. Himathongkam, Thep Front Endocrinol (Lausanne) Endocrinology Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) is characterized by asymptomatic, non-progressive and fasting hyperglycemia, albeit not without phenotypic variability. We used next generation sequencing (NGS) to screen for 34 MODY genes in a non-obese person with familial young-onset diabetes followed by screening in 24 family members within three generations with varying presentations of young-onset diabetes and sensorineural hearing loss. The index patient was found to carry a paternally-inherited heterozygous missense variant (c.716 A>G) of GCK in exon 7 with amino acid change (Q239R). This variant was associated with phenotypic heterogeneity ranging from normal glucose tolerance to diabetes with complications amongst the siblings which might be modified by obesity and chronic hepatitis B infection. Two paternally-inherited variants of SLC29A3 encoding a nucleoside transporter protein and Apo-A1 genes also co-segregated with glucose and lipid traits. Co-occurrence of diabetes and deafness in maternal aunts led to discovery of WFS1 (Wolfram syndrome type 1) as a cause of non-syndromic deafness in multiple members of the maternal pedigree. Our findings highlight the complex causes of familial young-onset diabetes and the need of a multidisciplinary approach to interpret the clinical relevance of discoveries made by NGS in this era of genomic medicine. Frontiers Media S.A. 2021-09-01 /pmc/articles/PMC8498575/ /pubmed/34630320 http://dx.doi.org/10.3389/fendo.2021.690343 Text en Copyright © 2021 Thewjitcharoen, Wanothayaroj, Krittiyawong, Nakasatien, Tsoi, Lim, Chan and Himathongkam https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Thewjitcharoen, Yotsapon
Wanothayaroj, Ekgaluck
Krittiyawong, Sirinate
Nakasatien, Soontaree
Tsoi, Tsz Fung
Lim, Cadmon K. P.
Chan, Juliana C. N.
Himathongkam, Thep
Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes
title Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes
title_full Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes
title_fullStr Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes
title_full_unstemmed Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes
title_short Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes
title_sort phenotypic and genetic heterogeneity in a thai glucokinase mody family reveals the complexity of young-onset diabetes
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498575/
https://www.ncbi.nlm.nih.gov/pubmed/34630320
http://dx.doi.org/10.3389/fendo.2021.690343
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