The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients
Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: <i>HNF4A</i>, <i&g...
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2021-01-01
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| author | Dinara E. Ivanoshchuk Elena V. Shakhtshneider Oksana D. Rymar Alla K. Ovsyannikova Svetlana V. Mikhailova Veniamin S. Fishman Emil S. Valeev Pavel S. Orlov Mikhail I. Voevoda |
| author_facet | Dinara E. Ivanoshchuk Elena V. Shakhtshneider Oksana D. Rymar Alla K. Ovsyannikova Svetlana V. Mikhailova Veniamin S. Fishman Emil S. Valeev Pavel S. Orlov Mikhail I. Voevoda |
| author_sort | Dinara E. Ivanoshchuk |
| collection | DOAJ |
| description | Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: <i>HNF4A</i>, <i>GCK</i>, <i>HNF1A</i>, <i>PDX1</i>, <i>HNF1B</i>, <i>NEUROD1</i>, <i>KLF11</i>, <i>CEL</i>, <i>PAX4</i>, <i>INS</i>, <i>BLK</i>, <i>KCNJ11</i>, <i>ABCC8</i>, and <i>APPL1</i>. The most common subtypes of MODY are associated with mutations in the genes <i>GCK</i>, <i>HNF1A</i>, <i>HNF4A</i>, and <i>HNF1B</i>. Among them, up to 70% of cases are caused by mutations in <i>GCK</i> and <i>HNF1A</i>. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in <i>HNF4A</i>, <i>GCK</i>, <i>HNF1A</i>, and <i>ABCC8</i>. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 −1G>T, Cys371*, and Glu443Lys in <i>GCK</i> and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in <i>HNF1A</i>. |
| first_indexed | 2024-03-09T04:28:54Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T04:28:54Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
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| series | Journal of Personalized Medicine |
| spelling | doaj.art-90bfcc74d5e84756be8d5bfa7afc41a22023-12-03T13:38:02ZengMDPI AGJournal of Personalized Medicine2075-44262021-01-011115710.3390/jpm11010057The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia PatientsDinara E. Ivanoshchuk0Elena V. Shakhtshneider1Oksana D. Rymar2Alla K. Ovsyannikova3Svetlana V. Mikhailova4Veniamin S. Fishman5Emil S. Valeev6Pavel S. Orlov7Mikhail I. Voevoda8Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaInstitute of Internal and Preventive Medicine—Branch of Institute of Cytology and Genetics, SB RAS, Bogatkova Str. 175/1, 630004 Novosibirsk, RussiaInstitute of Internal and Preventive Medicine—Branch of Institute of Cytology and Genetics, SB RAS, Bogatkova Str. 175/1, 630004 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, 630090 Novosibirsk, RussiaMaturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: <i>HNF4A</i>, <i>GCK</i>, <i>HNF1A</i>, <i>PDX1</i>, <i>HNF1B</i>, <i>NEUROD1</i>, <i>KLF11</i>, <i>CEL</i>, <i>PAX4</i>, <i>INS</i>, <i>BLK</i>, <i>KCNJ11</i>, <i>ABCC8</i>, and <i>APPL1</i>. The most common subtypes of MODY are associated with mutations in the genes <i>GCK</i>, <i>HNF1A</i>, <i>HNF4A</i>, and <i>HNF1B</i>. Among them, up to 70% of cases are caused by mutations in <i>GCK</i> and <i>HNF1A</i>. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in <i>HNF4A</i>, <i>GCK</i>, <i>HNF1A</i>, and <i>ABCC8</i>. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 −1G>T, Cys371*, and Glu443Lys in <i>GCK</i> and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in <i>HNF1A</i>.https://www.mdpi.com/2075-4426/11/1/57maturity onset diabetes of the youngMODYdiabetes mellitusmultiplex ligation-dependent probe amplificationnext-generation sequencingGCK |
| spellingShingle | Dinara E. Ivanoshchuk Elena V. Shakhtshneider Oksana D. Rymar Alla K. Ovsyannikova Svetlana V. Mikhailova Veniamin S. Fishman Emil S. Valeev Pavel S. Orlov Mikhail I. Voevoda The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients Journal of Personalized Medicine maturity onset diabetes of the young MODY diabetes mellitus multiplex ligation-dependent probe amplification next-generation sequencing GCK |
| title | The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients |
| title_full | The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients |
| title_fullStr | The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients |
| title_full_unstemmed | The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients |
| title_short | The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients |
| title_sort | mutation spectrum of maturity onset diabetes of the young mody associated genes among western siberia patients |
| topic | maturity onset diabetes of the young MODY diabetes mellitus multiplex ligation-dependent probe amplification next-generation sequencing GCK |
| url | https://www.mdpi.com/2075-4426/11/1/57 |
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