Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome
<p dir="ltr">Fanconi–Bickel Syndrome (FBS) is a rare disorder of carbohydrate metabolism that is characterized by the accumulation of glycogen mainly in the liver. It is inherited in an autosomal recessive manner due to mutations in the <i>SLC2A2</i> gene. <i>SLC2A2...
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2022
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| _version_ | 1864513506604220416 |
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| author | Sanaa Sharari (12561952) |
| author2 | Basirudeen Kabeer (18295432) Idris Mohammed (751020) Basma Haris (12040355) Igor Pavlovski (12561964) Iman Hawari (12561958) Ajaz Ahmad Bhat (12561955) Mohammed Toufiq (7251596) Sara Tomei (3441323) Rebecca Mathew (6561392) Najeeb Syed (12561967) Sabah Nisar (12561961) Selma Maacha (501715) Jean-Charles Grivel (284645) Damien Chaussabel (26369) Johan Ericsson (49714) Khalid Hussain (110443) |
| author2_role | author author author author author author author author author author author author author author author author |
| author_facet | Sanaa Sharari (12561952) Basirudeen Kabeer (18295432) Idris Mohammed (751020) Basma Haris (12040355) Igor Pavlovski (12561964) Iman Hawari (12561958) Ajaz Ahmad Bhat (12561955) Mohammed Toufiq (7251596) Sara Tomei (3441323) Rebecca Mathew (6561392) Najeeb Syed (12561967) Sabah Nisar (12561961) Selma Maacha (501715) Jean-Charles Grivel (284645) Damien Chaussabel (26369) Johan Ericsson (49714) Khalid Hussain (110443) |
| author_role | author |
| dc.creator.none.fl_str_mv | Sanaa Sharari (12561952) Basirudeen Kabeer (18295432) Idris Mohammed (751020) Basma Haris (12040355) Igor Pavlovski (12561964) Iman Hawari (12561958) Ajaz Ahmad Bhat (12561955) Mohammed Toufiq (7251596) Sara Tomei (3441323) Rebecca Mathew (6561392) Najeeb Syed (12561967) Sabah Nisar (12561961) Selma Maacha (501715) Jean-Charles Grivel (284645) Damien Chaussabel (26369) Johan Ericsson (49714) Khalid Hussain (110443) |
| dc.date.none.fl_str_mv | 2022-08-29T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/biomedicines10092114 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Understanding_the_Role_of_GLUT2_in_Dysglycemia_Associated_with_Fanconi_Bickel_Syndrome/26869528 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Fanconi–Bickel syndrome (FBS) dysglycemia glucose transporter 2 (GLUT2) PBMCs (peripheral blood mononuclear cells) miRNAs |
| dc.title.none.fl_str_mv | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Fanconi–Bickel Syndrome (FBS) is a rare disorder of carbohydrate metabolism that is characterized by the accumulation of glycogen mainly in the liver. It is inherited in an autosomal recessive manner due to mutations in the <i>SLC2A2</i> gene. <i>SLC2A2</i> encodes for the glucose transporter GLUT2 and is expressed in tissues that are involved in glucose homeostasis. The molecular mechanisms of dysglycemia in FBS are still not clearly understood. In this study, we report two cases of FBS with classical phenotypes of FBS associated with dysglycemia. Genomic DNA was extracted and analyzed by whole-genome and Sanger sequencing, and patient PBMCs were used for molecular analysis. One patient had an exonic <i>SLC2A2</i> mutation (c.1093C>T in exon 9, R365X), while the other patient had a novel intronic <i>SLC2A2</i> mutation (c.613-7T>G). Surprisingly, the exonic mutation resulted in the overexpression of dysfunctional GLUT2, resulting in the dysregulated expression of other glucose transporters. The intronic mutation did not affect the coding sequence of GLUT2, its expression, or glucose transport activity. However, it was associated with the expression of miRNAs correlated with type 1 diabetes mellitus, with a particular significant overexpression of hsa-miR-29a-3p implicated in insulin production and secretion. Our findings suggest that <i>SLC2A2</i> mutations cause dysglycemia in FBS either by a direct effect on GLUT2 expression and/or activity or, indirectly, by the dysregulated expression of miRNAs implicated in glucose homeostasis.</p><h2>Other Information</h2><p dir="ltr">Published in: Biomedicines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biomedicines10092114" target="_blank">https://dx.doi.org/10.3390/biomedicines10092114</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b95c2e8c90876f74c56260db07f167f5 |
| identifier_str_mv | 10.3390/biomedicines10092114 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26869528 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel SyndromeSanaa Sharari (12561952)Basirudeen Kabeer (18295432)Idris Mohammed (751020)Basma Haris (12040355)Igor Pavlovski (12561964)Iman Hawari (12561958)Ajaz Ahmad Bhat (12561955)Mohammed Toufiq (7251596)Sara Tomei (3441323)Rebecca Mathew (6561392)Najeeb Syed (12561967)Sabah Nisar (12561961)Selma Maacha (501715)Jean-Charles Grivel (284645)Damien Chaussabel (26369)Johan Ericsson (49714)Khalid Hussain (110443)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsFanconi–Bickel syndrome (FBS)dysglycemiaglucose transporter 2 (GLUT2)PBMCs (peripheral blood mononuclear cells)miRNAs<p dir="ltr">Fanconi–Bickel Syndrome (FBS) is a rare disorder of carbohydrate metabolism that is characterized by the accumulation of glycogen mainly in the liver. It is inherited in an autosomal recessive manner due to mutations in the <i>SLC2A2</i> gene. <i>SLC2A2</i> encodes for the glucose transporter GLUT2 and is expressed in tissues that are involved in glucose homeostasis. The molecular mechanisms of dysglycemia in FBS are still not clearly understood. In this study, we report two cases of FBS with classical phenotypes of FBS associated with dysglycemia. Genomic DNA was extracted and analyzed by whole-genome and Sanger sequencing, and patient PBMCs were used for molecular analysis. One patient had an exonic <i>SLC2A2</i> mutation (c.1093C>T in exon 9, R365X), while the other patient had a novel intronic <i>SLC2A2</i> mutation (c.613-7T>G). Surprisingly, the exonic mutation resulted in the overexpression of dysfunctional GLUT2, resulting in the dysregulated expression of other glucose transporters. The intronic mutation did not affect the coding sequence of GLUT2, its expression, or glucose transport activity. However, it was associated with the expression of miRNAs correlated with type 1 diabetes mellitus, with a particular significant overexpression of hsa-miR-29a-3p implicated in insulin production and secretion. Our findings suggest that <i>SLC2A2</i> mutations cause dysglycemia in FBS either by a direct effect on GLUT2 expression and/or activity or, indirectly, by the dysregulated expression of miRNAs implicated in glucose homeostasis.</p><h2>Other Information</h2><p dir="ltr">Published in: Biomedicines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biomedicines10092114" target="_blank">https://dx.doi.org/10.3390/biomedicines10092114</a></p>2022-08-29T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/biomedicines10092114https://figshare.com/articles/journal_contribution/Understanding_the_Role_of_GLUT2_in_Dysglycemia_Associated_with_Fanconi_Bickel_Syndrome/26869528CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/268695282022-08-29T09:00:00Z |
| spellingShingle | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome Sanaa Sharari (12561952) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Fanconi–Bickel syndrome (FBS) dysglycemia glucose transporter 2 (GLUT2) PBMCs (peripheral blood mononuclear cells) miRNAs |
| status_str | publishedVersion |
| title | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| title_full | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| title_fullStr | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| title_full_unstemmed | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| title_short | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| title_sort | Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Fanconi–Bickel syndrome (FBS) dysglycemia glucose transporter 2 (GLUT2) PBMCs (peripheral blood mononuclear cells) miRNAs |