Case Report: New insights about clinical manifestations of patients with GCK genetic variants
GCK-MODY is a genetic condition characterized by alterations in the GCK gene, which can include several types of inactivating genetic variants - ranging from missense and nonsense variants, and splice site variants, to small and large deletions and insertions in the gene. This disorder primarily aff...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1549279/full |
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| author | Ritiele Bastos de Souza Gabriella de Medeiros Abreu Gabriella de Medeiros Abreu Marília Chaves Bernardo Roberta Magalhães Tarantino Melanie Rodacki Lenita Zajdenverg Amanda Ferreira de Andrade Deborah Snaider Nicolay Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Kaio Cezar Rodrigues Salum Kaio Cezar Rodrigues Salum Renata Szundy Berardo Jorge Luiz Luescher Verônica Marques Zembrzuski Pedro Hernan Cabello Mario Campos Junior |
| author_facet | Ritiele Bastos de Souza Gabriella de Medeiros Abreu Gabriella de Medeiros Abreu Marília Chaves Bernardo Roberta Magalhães Tarantino Melanie Rodacki Lenita Zajdenverg Amanda Ferreira de Andrade Deborah Snaider Nicolay Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Kaio Cezar Rodrigues Salum Kaio Cezar Rodrigues Salum Renata Szundy Berardo Jorge Luiz Luescher Verônica Marques Zembrzuski Pedro Hernan Cabello Mario Campos Junior |
| author_sort | Ritiele Bastos de Souza |
| collection | DOAJ |
| description | GCK-MODY is a genetic condition characterized by alterations in the GCK gene, which can include several types of inactivating genetic variants - ranging from missense and nonsense variants, and splice site variants, to small and large deletions and insertions in the gene. This disorder primarily affects glucose homeostasis and usually presents in heterozygous individuals. Although GCK-MODY is a well-studied condition, some variant carriers may manifest symptoms that deviate from the typical disease phenotype. Our study identified two Brazilian patients with GCK-MODY carrying novel frameshift variants, one of whom presented atypical manifestations of the disease. The patient is a 14-year-old male harboring a variant c.398del; p.(Phe133SerfsTer7) in the GCK gene. He presented with the typical clinical features of GCK-MODY, including mild and stable fasting hyperglycemia, however, he also presented a history of polyuria and polydipsia, which are unusual symptoms of the disease. These symptoms could be associated with the more severe impact of a frameshift variant. However, we did not observe the same unusual phenotype in our second patient, who is a 15-year-old normal-weight female. At the age of 8, she was diagnosed with diabetes mellitus. The patient with the p.(Val335ArgfsTer124) variant presented with mild, stable hyperglycemia, a characteristic feature of the disease. In this study, we present two cases of novel frameshift variants in GCK and review other reports in the literature that have shown patients with atypical manifestations of the disease and highlight the importance of a comprehensive characterization of the phenotypic spectrum caused by GCK-MODY variants. |
| format | Article |
| id | doaj-art-dfd7380e7d324159a4dc2e19add4f435 |
| institution | OA Journals |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-dfd7380e7d324159a4dc2e19add4f4352025-08-20T02:16:05ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.15492791549279Case Report: New insights about clinical manifestations of patients with GCK genetic variantsRitiele Bastos de Souza0Gabriella de Medeiros Abreu1Gabriella de Medeiros Abreu2Marília Chaves Bernardo3Roberta Magalhães Tarantino4Melanie Rodacki5Lenita Zajdenverg6Amanda Ferreira de Andrade7Deborah Snaider Nicolay8Ana Carolina Proença da Fonseca9Ana Carolina Proença da Fonseca10Ana Carolina Proença da Fonseca11Ana Carolina Proença da Fonseca12Kaio Cezar Rodrigues Salum13Kaio Cezar Rodrigues Salum14Renata Szundy Berardo15Jorge Luiz Luescher16Verônica Marques Zembrzuski17Pedro Hernan Cabello18Mario Campos Junior19Laboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilJosué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilDiabetes and Nutrology Section, Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilDiabetes and Nutrology Section, Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilDiabetes and Nutrology Section, Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilDiabetes and Nutrology Section, Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilGenetics Laboratory, Grande Rio University/AFYA, Rio de Janeiro, BrazilPostgraduate Program in Translational Biomedicine, Grande Rio University/AFYA, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilClementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilPediatric Endocrinology Section, Federal Hospital of State Servants, Rio de Janeiro, BrazilMartagão Gesteira Child Care and Pediatrics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilGCK-MODY is a genetic condition characterized by alterations in the GCK gene, which can include several types of inactivating genetic variants - ranging from missense and nonsense variants, and splice site variants, to small and large deletions and insertions in the gene. This disorder primarily affects glucose homeostasis and usually presents in heterozygous individuals. Although GCK-MODY is a well-studied condition, some variant carriers may manifest symptoms that deviate from the typical disease phenotype. Our study identified two Brazilian patients with GCK-MODY carrying novel frameshift variants, one of whom presented atypical manifestations of the disease. The patient is a 14-year-old male harboring a variant c.398del; p.(Phe133SerfsTer7) in the GCK gene. He presented with the typical clinical features of GCK-MODY, including mild and stable fasting hyperglycemia, however, he also presented a history of polyuria and polydipsia, which are unusual symptoms of the disease. These symptoms could be associated with the more severe impact of a frameshift variant. However, we did not observe the same unusual phenotype in our second patient, who is a 15-year-old normal-weight female. At the age of 8, she was diagnosed with diabetes mellitus. The patient with the p.(Val335ArgfsTer124) variant presented with mild, stable hyperglycemia, a characteristic feature of the disease. In this study, we present two cases of novel frameshift variants in GCK and review other reports in the literature that have shown patients with atypical manifestations of the disease and highlight the importance of a comprehensive characterization of the phenotypic spectrum caused by GCK-MODY variants.https://www.frontiersin.org/articles/10.3389/fendo.2025.1549279/fullmonogenic diabetesGCK-MODYglucokinasescreeningatypical symptoms |
| spellingShingle | Ritiele Bastos de Souza Gabriella de Medeiros Abreu Gabriella de Medeiros Abreu Marília Chaves Bernardo Roberta Magalhães Tarantino Melanie Rodacki Lenita Zajdenverg Amanda Ferreira de Andrade Deborah Snaider Nicolay Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Kaio Cezar Rodrigues Salum Kaio Cezar Rodrigues Salum Renata Szundy Berardo Jorge Luiz Luescher Verônica Marques Zembrzuski Pedro Hernan Cabello Mario Campos Junior Case Report: New insights about clinical manifestations of patients with GCK genetic variants Frontiers in Endocrinology monogenic diabetes GCK-MODY glucokinase screening atypical symptoms |
| title | Case Report: New insights about clinical manifestations of patients with GCK genetic variants |
| title_full | Case Report: New insights about clinical manifestations of patients with GCK genetic variants |
| title_fullStr | Case Report: New insights about clinical manifestations of patients with GCK genetic variants |
| title_full_unstemmed | Case Report: New insights about clinical manifestations of patients with GCK genetic variants |
| title_short | Case Report: New insights about clinical manifestations of patients with GCK genetic variants |
| title_sort | case report new insights about clinical manifestations of patients with gck genetic variants |
| topic | monogenic diabetes GCK-MODY glucokinase screening atypical symptoms |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1549279/full |
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