A Comprehensive Analysis of Hungarian MODY Patients—Part I: Gene Panel Sequencing Reveals Pathogenic Mutations in HNF1A, HNF1B, HNF4A, ABCC8 and INS Genes
Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested...
Saved in:
| Published in | Life (Basel, Switzerland) Vol. 11; no. 8; p. 755 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel
MDPI AG
27.07.2021
MDPI |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2075-1729 2075-1729 |
| DOI | 10.3390/life11080755 |
Cover
| Abstract | Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment. |
|---|---|
| AbstractList | Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being
HNF1A, HNF4A, HNF1B
and
GCK
. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the
GCK
gene, about 20% in the
HNF1A
gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the
HNF1A
gene in a total of 48 patients and family members. In the case of
HNF1A
-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment. Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment. Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment.Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment. |
| Author | Kántor, Irén Balogh, István Karádi, Zsuzsanna Felszeghy, Enikő Tóth-Heyn, Péter Szűcs, Zsuzsanna Madar, László Gaál, Zsolt Benn, Orsolya Luczay, Andrea |
| AuthorAffiliation | 3 Department of Pediatrics, Jósa András Teaching Hospital, 4400 Nyíregyháza, Hungary; kantoriren@index.hu 4 1st Department of Pediatrics, Semmelweis University, 1085 Budapest, Hungary; luczay.andrea@med.semmelweis-univ.hu (A.L.); toth-heyn.peter@med.semmelweis-univ.hu (P.T.-H.) 5 Department of Pediatrics, Szent György Hospital of Fejér County, 8000 Székesfehérvár, Hungary; bennorsolya@gmail.com (O.B.); zskaradi@mail.fmkorhaz.hu (Z.K.) 1 4th Department of Medicine, Jósa András Teaching Hospital, 4400 Nyíregyháza, Hungary; dr.gaal.zsolt@szszbmk.hu 6 Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; felszeghy.eniko@med.unideb.hu 2 Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; szucs.zsuzsanna@med.unideb.hu (Z.S.); madar.laszlo@med.unideb.hu (L.M.) |
| AuthorAffiliation_xml | – name: 3 Department of Pediatrics, Jósa András Teaching Hospital, 4400 Nyíregyháza, Hungary; kantoriren@index.hu – name: 2 Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; szucs.zsuzsanna@med.unideb.hu (Z.S.); madar.laszlo@med.unideb.hu (L.M.) – name: 4 1st Department of Pediatrics, Semmelweis University, 1085 Budapest, Hungary; luczay.andrea@med.semmelweis-univ.hu (A.L.); toth-heyn.peter@med.semmelweis-univ.hu (P.T.-H.) – name: 6 Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; felszeghy.eniko@med.unideb.hu – name: 5 Department of Pediatrics, Szent György Hospital of Fejér County, 8000 Székesfehérvár, Hungary; bennorsolya@gmail.com (O.B.); zskaradi@mail.fmkorhaz.hu (Z.K.) – name: 1 4th Department of Medicine, Jósa András Teaching Hospital, 4400 Nyíregyháza, Hungary; dr.gaal.zsolt@szszbmk.hu |
| Author_xml | – sequence: 1 givenname: Zsolt surname: Gaál fullname: Gaál, Zsolt – sequence: 2 givenname: Zsuzsanna orcidid: 0000-0003-2836-3383 surname: Szűcs fullname: Szűcs, Zsuzsanna – sequence: 3 givenname: Irén surname: Kántor fullname: Kántor, Irén – sequence: 4 givenname: Andrea surname: Luczay fullname: Luczay, Andrea – sequence: 5 givenname: Péter surname: Tóth-Heyn fullname: Tóth-Heyn, Péter – sequence: 6 givenname: Orsolya surname: Benn fullname: Benn, Orsolya – sequence: 7 givenname: Enikő surname: Felszeghy fullname: Felszeghy, Enikő – sequence: 8 givenname: Zsuzsanna surname: Karádi fullname: Karádi, Zsuzsanna – sequence: 9 givenname: László surname: Madar fullname: Madar, László – sequence: 10 givenname: István orcidid: 0000-0003-3397-2829 surname: Balogh fullname: Balogh, István |
| BookMark | eNptks1uEzEQx1eoiJbSGw9giQuHBvyx9q45IKWBNpH6JQoHTpbjnd042tjB3o3UWx-iR56OJ8HZFKmt8GXs8X9-o_l4ne057yDL3hL8gTGJP7a2BkJwiQvOX2QHNNkRKajce3Tfz45iXOJ0BCeizF9l-yzPc5xLeZD9HqOJX60DLMBFuwE0drq9jTYiX6Np7xodrHbo4urLT3StOwuui3_u7q916NDsEzoDB8nvoEU38KsHZ6xr0DfYgG7jNmDhG3DWoIu-S9HeRWQdml6ekvHxYE4Gk6fX-GQyKZF2FZpd3gzg-CZ7WScOHD3Yw-zH6dfvk-no_OpsNhmfj0zOeTeaM8F1CZhTU-hyLrEocYVJgQ0DqLQpNZEgBNUVMcxwCqLgtDCGUaiJIcAOs9mOW3m9VOtgVzrcKq-tGhw-NCrVa00LitZSi1qmrtM8r3k5p7omJaU4wbkxMrE-71jrfr6CyqSGBd0-gT79cXahGr9RJZMSS5IA7x8AwaeOxk6tbDTQtqnLvo-KciEwLXK8zfXumXTp-5AGOKg4o4WgLKnoTmWCjzFArYzdDSPlt60iWG13ST3epRR0_CzoXwX_lf8FbkHKDA |
| CitedBy_id | crossref_primary_10_3389_fgene_2023_1132772 crossref_primary_10_3390_biom15030414 crossref_primary_10_3389_fonc_2022_1011230 crossref_primary_10_3390_jpm12111762 crossref_primary_10_1007_s40200_022_00975_8 |
| Cites_doi | 10.1007/s00424-006-0112-3 10.1507/endocrj.50.491 10.1111/j.1399-5448.2011.00827.x 10.1038/gim.2015.30 10.1111/dme.12992 10.1111/pedi.12532 10.1073/pnas.241349398 10.1038/384455a0 10.2478/enr-2019-0013 10.1111/pedi.12289 10.1681/ASN.2008060633 10.1111/j.1464-5491.2009.02913.x 10.1016/j.ymgme.2014.09.007 10.21203/rs.2.11834/v1 10.1111/pedi.12032 10.1007/s00125-008-0942-y 10.2337/dc08-2018 10.2337/db07-0859 10.1556/650.2016.30399 10.1002/(SICI)1096-9136(199801)15:1<15::AID-DIA562>3.0.CO;2-M 10.12701/yujm.2019.00409 10.3389/fendo.2018.00253 10.4997/JRCPE.2011.205 10.1007/s00125-002-0814-9 10.1111/1753-0407.13097 10.2337/diab.46.4.720 10.5001/omj.2020.44 10.2337/db12-0880 10.2337/diab.24.1.44 10.1080/14737159.2020.1730179 10.1111/pedi.12931 10.1111/j.1464-5491.2006.01999.x 10.1007/s001250051025 10.1073/pnas.94.24.13209 10.1016/j.beem.2018.06.008 10.2337/diabetes.51.8.2355 10.1093/hmg/6.4.583 10.2337/diab.46.4.726 10.1007/s001250051101 10.1038/ki.2014.202 10.2337/dc07-1785 10.1371/journal.pone.0037423 10.1210/er.2007-0024 10.1586/erm.10.123 10.1046/j.1464-5491.2001.00447.x |
| ContentType | Journal Article |
| Copyright | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2021 by the authors. 2021 |
| Copyright_xml | – notice: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2021 by the authors. 2021 |
| DBID | AAYXX CITATION 8FD 8FE 8FH ABUWG AEUYN AFKRA ATCPS AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FR3 GNUQQ HCIFZ LK8 M7P P64 PATMY PHGZM PHGZT PIMPY PKEHL PQEST PQGLB PQQKQ PQUKI PRINS PYCSY RC3 7X8 5PM DOA |
| DOI | 10.3390/life11080755 |
| DatabaseName | CrossRef Technology Research Database ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Central (Alumni) ProQuest One Sustainability ProQuest Central UK/Ireland Agricultural & Environmental Science Collection ProQuest Central Essentials Biological Science Collection AUTh Library subscriptions: ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Engineering Research Database ProQuest Central Student SciTech Premium Collection (Proquest) Biological Sciences Biological Science Database (Proquest) Biotechnology and BioEngineering Abstracts Environmental Science Database ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database (Proquest) ProQuest One Academic Middle East (New) ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China Environmental Science Collection Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) Open Access: DOAJ - Directory of Open Access Journals |
| DatabaseTitle | CrossRef Publicly Available Content Database ProQuest Central Student Technology Research Database ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest One Sustainability Genetics Abstracts Natural Science Collection ProQuest Central Korea Agricultural & Environmental Science Collection Biological Science Collection ProQuest Central (New) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition Biological Science Database ProQuest SciTech Collection Biotechnology and BioEngineering Abstracts Environmental Science Collection ProQuest One Academic UKI Edition Environmental Science Database Engineering Research Database ProQuest One Academic ProQuest One Academic (New) MEDLINE - Academic |
| DatabaseTitleList | CrossRef Publicly Available Content Database MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Open Access Full Text url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: BENPR name: ProQuest Central url: http://www.proquest.com/pqcentral?accountid=15518 sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 2075-1729 |
| ExternalDocumentID | oai_doaj_org_article_2f9a6f9fe1244f58b2af18220ad15cc9 PMC8399091 10_3390_life11080755 |
| GeographicLocations | United States--US Germany |
| GeographicLocations_xml | – name: United States--US – name: Germany |
| GroupedDBID | 53G 5VS 7XC 8FE 8FH AADQD AAFWJ AAYXX ABDBF ACUHS ADBBV AEUYN AFKRA AFPKN AFZYC ALMA_UNASSIGNED_HOLDINGS AOIJS ATCPS BAWUL BBNVY BCNDV BENPR BHPHI CCPQU CITATION DIK ESX GROUPED_DOAJ HCIFZ HYE IAO IEP ISR ITC KQ8 LK8 M48 M7P MODMG M~E OK1 PATMY PGMZT PHGZM PHGZT PIMPY PROAC PYCSY RPM 8FD ABUWG AZQEC DWQXO FR3 GNUQQ P64 PKEHL PQEST PQGLB PQQKQ PQUKI PRINS RC3 7X8 PUEGO 5PM |
| ID | FETCH-LOGICAL-c455t-b365a8e052c7a8b90680d0170c3eedac8a19e662ad1c3c52e67527cc32ef1c1e3 |
| IEDL.DBID | M48 |
| ISSN | 2075-1729 |
| IngestDate | Wed Aug 27 01:28:28 EDT 2025 Thu Aug 21 18:38:46 EDT 2025 Fri Sep 05 03:33:46 EDT 2025 Fri Jul 25 10:38:44 EDT 2025 Thu Apr 24 23:04:57 EDT 2025 Tue Jul 01 04:09:35 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 8 |
| Language | English |
| License | https://creativecommons.org/licenses/by/4.0 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c455t-b365a8e052c7a8b90680d0170c3eedac8a19e662ad1c3c52e67527cc32ef1c1e3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0003-3397-2829 0000-0003-2836-3383 |
| OpenAccessLink | http://journals.scholarsportal.info/openUrl.xqy?doi=10.3390/life11080755 |
| PMID | 34440499 |
| PQID | 2565327623 |
| PQPubID | 2032373 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_2f9a6f9fe1244f58b2af18220ad15cc9 pubmedcentral_primary_oai_pubmedcentral_nih_gov_8399091 proquest_miscellaneous_2566027409 proquest_journals_2565327623 crossref_citationtrail_10_3390_life11080755 crossref_primary_10_3390_life11080755 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 20210727 |
| PublicationDateYYYYMMDD | 2021-07-27 |
| PublicationDate_xml | – month: 7 year: 2021 text: 20210727 day: 27 |
| PublicationDecade | 2020 |
| PublicationPlace | Basel |
| PublicationPlace_xml | – name: Basel |
| PublicationTitle | Life (Basel, Switzerland) |
| PublicationYear | 2021 |
| Publisher | MDPI AG MDPI |
| Publisher_xml | – name: MDPI AG – name: MDPI |
| References | Yamagata (ref_24) 2003; 50 Carmody (ref_3) 2014; 113 Vaxillaire (ref_35) 1997; 6 Shepherd (ref_22) 2001; 18 Hani (ref_34) 1998; 41 Steele (ref_20) 2010; 27 ref_51 Richards (ref_30) 2015; 17 Tatsi (ref_50) 2020; 21 Stoffel (ref_23) 1997; 94 Azriel (ref_38) 2011; 17 Richards (ref_29) 2008; 10 Frayling (ref_33) 1997; 46 Rafiq (ref_42) 2008; 31 Tattersall (ref_6) 1974; 43 Boj (ref_12) 2001; 98 Thanabalasingham (ref_39) 2013; 62 Chambers (ref_13) 2016; 17 Tattersall (ref_7) 1975; 24 Xu (ref_36) 2002; 45 Barbetti (ref_1) 2018; 32 Carette (ref_16) 2008; 57 Yamagata (ref_40) 1996; 384 Campbell (ref_4) 2020; 20 Jermendy (ref_45) 2016; 157 Lorini (ref_48) 2009; 32 Dalgaard (ref_32) 1998; 41 Girard (ref_46) 2006; 453 Molven (ref_11) 2011; 11 ref_31 Karaoglan (ref_14) 2020; 13 Tatsi (ref_49) 2013; 14 Jang (ref_19) 2020; 37 Losekoot (ref_5) 2016; 74 Thethy (ref_8) 2011; 41 Ferrer (ref_15) 2002; 51 Edghill (ref_28) 2006; 23 Firdous (ref_2) 2018; 9 Borowiec (ref_47) 2018; 19 Adalat (ref_26) 2009; 20 Hansen (ref_41) 1997; 46 Valkovicova (ref_17) 2019; 53 Bordier (ref_44) 2010; 31 Vaxillaire (ref_10) 2008; 29 Hattersley (ref_37) 1998; 15 Yorifuji (ref_43) 2012; 13 Yahaya (ref_9) 2020; 35 Bacon (ref_25) 2015; 33 Balogh (ref_21) 2019; 111 Faguer (ref_27) 2014; 86 Ellard (ref_18) 2008; 51 |
| References_xml | – volume: 453 start-page: 323 year: 2006 ident: ref_46 article-title: Functional Analysis of Six Kir6.2 (KCNJ11) Mutations Causing Neonatal Diabetes publication-title: Pflugers Arch. doi: 10.1007/s00424-006-0112-3 – volume: 50 start-page: 491 year: 2003 ident: ref_24 article-title: Regulation of Pancreatic β-Cell Function by the HNF Transcription Network: Lessons from Maturity-Onset Diabetes of the Young (MODY) publication-title: Endocr. J. doi: 10.1507/endocrj.50.491 – volume: 13 start-page: 26 year: 2012 ident: ref_43 article-title: Comprehensive Molecular Analysis of Japanese Patients with Pediatric-Onset MODY-Type Diabetes Mellitus publication-title: Pediatr. Diabetes doi: 10.1111/j.1399-5448.2011.00827.x – volume: 17 start-page: 405 year: 2015 ident: ref_30 article-title: Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology publication-title: Genet. Med. doi: 10.1038/gim.2015.30 – volume: 33 start-page: 976 year: 2015 ident: ref_25 article-title: Successful Maintenance on Sulphonylurea Therapy and Low Diabetes Complication Rates in a HNF1A-MODY Cohort publication-title: Diabet. Med. J. Br. Diabet. Assoc. doi: 10.1111/dme.12992 – volume: 19 start-page: 53 year: 2018 ident: ref_47 article-title: Monogenic Diabetes Prevalence among Polish Children—Summary of 11 Years-Long Nationwide Genetic Screening Program publication-title: Pediatr. Diabetes doi: 10.1111/pedi.12532 – volume: 98 start-page: 14481 year: 2001 ident: ref_12 article-title: A Transcription Factor Regulatory Circuit in Differentiated Pancreatic Cells publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.241349398 – volume: 384 start-page: 455 year: 1996 ident: ref_40 article-title: Mutations in the Hepatocyte Nuclear Factor-1alpha Gene in Maturity-Onset Diabetes of the Young (MODY3) publication-title: Nature doi: 10.1038/384455a0 – volume: 43 start-page: 339 year: 1974 ident: ref_6 article-title: Mild Familial Diabetes with Dominant Inheritance publication-title: Q. J. Med. – volume: 53 start-page: 110 year: 2019 ident: ref_17 article-title: Novel Insights into Genetics and Clinics of the HNF1A-MODY publication-title: Endocr. Regul. doi: 10.2478/enr-2019-0013 – volume: 17 start-page: 360 year: 2016 ident: ref_13 article-title: Characteristics of Maturity Onset Diabetes of the Young in a Large Diabetes Center publication-title: Pediatr. Diabetes doi: 10.1111/pedi.12289 – volume: 20 start-page: 1123 year: 2009 ident: ref_26 article-title: HNF1B Mutations Associate with Hypomagnesemia and Renal Magnesium Wasting publication-title: J. Am. Soc. Nephrol. doi: 10.1681/ASN.2008060633 – volume: 27 start-page: 157 year: 2010 ident: ref_20 article-title: Increased All-Cause and Cardiovascular Mortality in Monogenic Diabetes as a Result of Mutations in the HNF1A Gene publication-title: Diabet. Med. doi: 10.1111/j.1464-5491.2009.02913.x – volume: 113 start-page: 315 year: 2014 ident: ref_3 article-title: Phenotypic Heterogeneity in Monogenic Diabetes: The Clinical and Diagnostic Utility of a Gene Panel-Based next-Generation Sequencing Approach publication-title: Mol. Genet. Metab. doi: 10.1016/j.ymgme.2014.09.007 – ident: ref_31 doi: 10.21203/rs.2.11834/v1 – volume: 14 start-page: 526 year: 2013 ident: ref_49 article-title: The Spectrum of HNF1A Gene Mutations in Greek Patients with MODY3: Relative Frequency and Identification of Seven Novel Germline Mutations publication-title: Pediatr. Diabetes doi: 10.1111/pedi.12032 – volume: 51 start-page: 546 year: 2008 ident: ref_18 article-title: European Molecular Genetics Quality Network (EMQN) MODY group Best Practice Guidelines for the Molecular Genetic Diagnosis of Maturity-Onset Diabetes of the Young publication-title: Diabetologia doi: 10.1007/s00125-008-0942-y – volume: 32 start-page: 1864 year: 2009 ident: ref_48 article-title: Maturity-Onset Diabetes of the Young in Children with Incidental Hyperglycemia: A Multicenter Italian Study of 172 Families publication-title: Diabetes Care doi: 10.2337/dc08-2018 – volume: 57 start-page: 503 year: 2008 ident: ref_16 article-title: The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3 publication-title: Diabetes doi: 10.2337/db07-0859 – volume: 157 start-page: 469 year: 2016 ident: ref_45 article-title: HNF-4-α-mutáció okozta monogénes diabetes mellitus (MODY-1) első hazai esete publication-title: Orv. Hetil. doi: 10.1556/650.2016.30399 – volume: 15 start-page: 15 year: 1998 ident: ref_37 article-title: Maturity-Onset Diabetes of the Young: Clinical Heterogeneity Explained by Genetic Heterogeneity publication-title: Diabet. Med. J. Br. Diabet. Assoc. doi: 10.1002/(SICI)1096-9136(199801)15:1<15::AID-DIA562>3.0.CO;2-M – volume: 37 start-page: 13 year: 2020 ident: ref_19 article-title: Maturity-Onset Diabetes of the Young: Update and Perspectives on Diagnosis and Treatment publication-title: Yeungnam Univ. J. Med. doi: 10.12701/yujm.2019.00409 – volume: 9 start-page: 253 year: 2018 ident: ref_2 article-title: Genetic Testing of Maturity-Onset Diabetes of the Young Current Status and Future Perspectives publication-title: Front. Endocrinol. doi: 10.3389/fendo.2018.00253 – volume: 41 start-page: 119 year: 2011 ident: ref_8 article-title: Diagnosis in Diabetes: Does It Matter? publication-title: J. R. Coll. Physicians Edinb. doi: 10.4997/JRCPE.2011.205 – volume: 31 start-page: e5 year: 2010 ident: ref_44 article-title: Type 2 diabetes mellitus associated with pancreatic and renal malformations publication-title: Rev. Med. Interne – volume: 45 start-page: 744 year: 2002 ident: ref_36 article-title: Mutations in the Hepatocyte Nuclear Factor-1alpha Gene in Chinese MODY Families: Prevalence and Functional Analysis publication-title: Diabetologia doi: 10.1007/s00125-002-0814-9 – volume: 13 start-page: 154 year: 2020 ident: ref_14 article-title: Clinical and Laboratory Clues of Maturity-Onset Diabetes of the Young and Determination of Association with Molecular Diagnosis publication-title: J. Diabetes doi: 10.1111/1753-0407.13097 – volume: 46 start-page: 720 year: 1997 ident: ref_33 article-title: Mutations in the Hepatocyte Nuclear Factor-1alpha Gene Are a Common Cause of Maturity-Onset Diabetes of the Young in the UK publication-title: Diabetes doi: 10.2337/diab.46.4.720 – volume: 111 start-page: 385 year: 2019 ident: ref_21 article-title: Monogenic Forms of Diabetes Mellitus publication-title: Exp. Suppl. – volume: 35 start-page: e126 year: 2020 ident: ref_9 article-title: Genetics and Pathophysiology of Maturity-Onset Diabetes of the Young (MODY): A Review of Current Trends publication-title: Oman Med. J. doi: 10.5001/omj.2020.44 – volume: 10 start-page: 294 year: 2008 ident: ref_29 article-title: Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations: Revisions 2007 publication-title: Genet. Med. Off. J. Am. Coll. Med. Genet. – volume: 62 start-page: 1329 year: 2013 ident: ref_39 article-title: Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile publication-title: Diabetes doi: 10.2337/db12-0880 – volume: 24 start-page: 44 year: 1975 ident: ref_7 article-title: A Difference between the Inheritance of Classical Juvenile-Onset and Maturity-Onset Type Diabetes of Young People publication-title: Diabetes doi: 10.2337/diab.24.1.44 – volume: 20 start-page: 413 year: 2020 ident: ref_4 article-title: Review of Current Status of Molecular Diagnosis and Characterization of Monogenic Diabetes Mellitus: A Focus on next-Generation Sequencing publication-title: Expert Rev. Mol. Diagn. doi: 10.1080/14737159.2020.1730179 – volume: 17 start-page: 256 year: 2011 ident: ref_38 article-title: Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation publication-title: Mol. Med. Camb. Mass – volume: 21 start-page: 28 year: 2020 ident: ref_50 article-title: Next Generation Sequencing Targeted Gene Panel in Greek MODY Patients Increases Diagnostic Accuracy publication-title: Pediatr. Diabetes doi: 10.1111/pedi.12931 – volume: 23 start-page: 1301 year: 2006 ident: ref_28 article-title: Hepatocyte Nuclear Factor-1 Beta Mutations Cause Neonatal Diabetes and Intrauterine Growth Retardation: Support for a Critical Role of HNF-1β in Human Pancreatic Development publication-title: Diabet. Med. doi: 10.1111/j.1464-5491.2006.01999.x – volume: 41 start-page: 1017 year: 1998 ident: ref_34 article-title: Mutation Screening in 18 Caucasian Families Suggest the Existence of Other MODY Genes publication-title: Diabetologia doi: 10.1007/s001250051025 – volume: 94 start-page: 13209 year: 1997 ident: ref_23 article-title: The Maturity-Onset Diabetes of the Young (MODY1) Transcription Factor HNF4α Regulates Expression of Genes Required for Glucose Transport and Metabolism publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.94.24.13209 – volume: 32 start-page: 575 year: 2018 ident: ref_1 article-title: Genetic Causes and Treatment of Neonatal Diabetes and Early Childhood Diabetes publication-title: Best Pract. Res. Clin. Endocrinol. Metab. doi: 10.1016/j.beem.2018.06.008 – volume: 51 start-page: 2355 year: 2002 ident: ref_15 article-title: A Genetic Switch in Pancreatic β-Cells: Implications for Differentiation and Haploinsufficiency publication-title: Diabetes doi: 10.2337/diabetes.51.8.2355 – volume: 6 start-page: 583 year: 1997 ident: ref_35 article-title: Identification of Nine Novel Mutations in the Hepatocyte Nuclear Factor 1 Alpha Gene Associated with Maturity-Onset Diabetes of the Young (MODY3) publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/6.4.583 – volume: 46 start-page: 726 year: 1997 ident: ref_41 article-title: Novel MODY3 Mutations in the Hepatocyte Nuclear Factor-1alpha Gene: Evidence for a Hyperexcitability of Pancreatic Beta-Cells to Intravenous Secretagogues in a Glucose-Tolerant Carrier of a P447L Mutation publication-title: Diabetes doi: 10.2337/diab.46.4.726 – volume: 41 start-page: 1528 year: 1998 ident: ref_32 article-title: Mutations in the Hepatocyte Nuclear Factor-1alpha Gene in Caucasian Families Originally Classified as Having Type I Diabetes publication-title: Diabetologia doi: 10.1007/s001250051101 – volume: 86 start-page: 1007 year: 2014 ident: ref_27 article-title: The HNF1B Score Is a Simple Tool to Select Patients for HNF1B Gene Analysis publication-title: Kidney Int. doi: 10.1038/ki.2014.202 – volume: 31 start-page: 204 year: 2008 ident: ref_42 article-title: Neonatal Diabetes International Collaborative Group Effective Treatment with Oral Sulfonylureas in Patients with Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations publication-title: Diabetes Care doi: 10.2337/dc07-1785 – ident: ref_51 doi: 10.1371/journal.pone.0037423 – volume: 74 start-page: 193 year: 2016 ident: ref_5 article-title: Maturity Onset Diabetes of the Young: Seek and You Will Find publication-title: Neth. J. Med. – volume: 29 start-page: 254 year: 2008 ident: ref_10 article-title: Monogenic Diabetes in the Young, Pharmacogenetics and Relevance to Multifactorial Forms of Type 2 Diabetes publication-title: Endocr. Rev. doi: 10.1210/er.2007-0024 – volume: 11 start-page: 313 year: 2011 ident: ref_11 article-title: Role of Molecular Genetics in Transforming Diagnosis of Diabetes Mellitus publication-title: Expert Rev. Mol. Diagn. doi: 10.1586/erm.10.123 – volume: 18 start-page: 417 year: 2001 ident: ref_22 article-title: Predictive Genetic Testing in Maturity-Onset Diabetes of the Young (MODY) publication-title: Diabet. Med. doi: 10.1046/j.1464-5491.2001.00447.x |
| SSID | ssj0000651684 |
| Score | 2.2411656 |
| Snippet | Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype... Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK . The... |
| SourceID | doaj pubmedcentral proquest crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Enrichment Source Index Database |
| StartPage | 755 |
| SubjectTerms | Age Diabetes Diabetes mellitus Diagnosis Families & family life Gene sequencing Genes Genetic screening Glucose Hepatocyte nuclear factor 4 HNF1A HNF1a gene Hyperglycemia Insulin Metabolism MODY monogenic diabetes Mutation Next-generation sequencing NGS Patients Phenotypes Sulfonylurea transcription factor MODY Transcription factors |
| SummonAdditionalLinks | – databaseName: Open Access: DOAJ - Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Pb9MwFLfQpElcEAwQZQMZCU4QzbFjx9mtLVQdUsvEmDROke3YaqUqRUuLtNs-xI58Oj4Jz3ZaJQfEhVOU5MXyn_f8fk9--T2E3sJ2JzxreaKpNElWUZZoSXRChBU6hV1TBwLT2VxMr7LP1_y6U-rL54RFeuA4cafUFUq4wlnviByXmioHmJgSVaXcmPDrHilIJ5iKezBPhcxipjuDuP50tYQmfEJd7v_q6_igQNXfw5f97MiOu5k8Ro9anIiHsX9P0ANbH6HDWDny9in6NcTekm_sIiag4x25CF47PAUDhhBY1Xj25eN3fBGpU5vfd_cXMF58foY92TQ8r-0KX8ZcavBg-Kv9CbCx8R8s1qBYS4Nn23hU3-BljafzSTr8EC6jcMngbjgajyVWdYXP55eh4eYZupp8-jaeJm2hhcRknG8SzQRX0hJOTa6kLnw9jsoT6xgGLlQZqdLCCkFhyg0znFqIMmhuDKPWpSa17Dk6qNe1fYGwBDjAs1xB2K0y4grNVU6r1FmIm7SScoDe76a-NC0LuS-GsSohGvELVXYXaoDe7aV_RPaNv8iN_CruZTxndngAmlS2mlT-S5MG6GSnA2VryE0JiJAzCh6DDdCb_WswQX-uAsu03gYZ4aN7Ak3kPd3pdaj_pl4uApk3ANQCMNvL_zGCY_SQ-pQbkic0P0EHm5utfQWYaaNfB_P4A3QMFIw priority: 102 providerName: Directory of Open Access Journals – databaseName: AUTh Library subscriptions: ProQuest Central dbid: BENPR link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1bb9MwFLZGJyReEFdRGMhI8ATWEid2HCSE2rKqQ2qoNiaNp8h2bFqpSkbTIvHGj-CRX8cv4dhJyvIAT1Yc27mce3zyHYRegLrjDrWcKCo0iQsaESUCRQJuuApBayoPYDrP-Owi_nDJLg9Q1v0L49IqO53oFXVRafeN_BhMM4soiG707uorcVWj3O5qV0JDtqUVirceYuwGOgSVzIIBOhyfZIuz_VcXMLghF3GTAR9BvH-8XlnjUuHBdLKebfIQ_j2_s581ec0MTe-g263_iEcNwe-iA1PeQzebipLf76NfI-wkfGOWTWI67kBHcGXxDAQbQmNZ4vnH95_xooFUrX__-LkABsKnb7ADoYb-0qzxeZNjDZYNn5lv4E7WbsKyAoZbaTzfNVv4NV6VeJZNw9Fr34x9E8PRaDyZCCzLAp9m537h-gG6mJ58msxIW4CB6JixLVERZ1KYgFGdSKFSV6ejcIA7OgLTKrWQYWo4p7IIdaQZNRB90ETriBob6tBED9GgrErzCGEBbgKLEwnhuIwDmyomE1qE1kA8paQQQ_Sqe_W5btHJXZGMdQ5RiiNUfp1QQ_RyP_qqQeX4x7ixo-J-jMPS9h3V5kveimZObSq5TWEWuDqWCUWlhaiLBvBYTOt0iI46HshbAa_zv-w4RM_3p0E03X4LkKna-THcRf0BLJH0eKd3Q_0z5WrpQb7BcU3Bl3v8_4s_QbeoS7IJEkKTIzTYbnbmKXhJW_WsZf0_6zcSHw priority: 102 providerName: ProQuest |
| Title | A Comprehensive Analysis of Hungarian MODY Patients—Part I: Gene Panel Sequencing Reveals Pathogenic Mutations in HNF1A, HNF1B, HNF4A, ABCC8 and INS Genes |
| URI | https://www.proquest.com/docview/2565327623 https://www.proquest.com/docview/2566027409 https://pubmed.ncbi.nlm.nih.gov/PMC8399091 https://doaj.org/article/2f9a6f9fe1244f58b2af18220ad15cc9 |
| Volume | 11 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1db9MwFLXGJiRe0PgShVEZCZ4gkDix4yAh1JZVHVJLtVFpPEW2Y6-VqoQ1LWJv_Ig97tftl-zaSapFfDxFTeykzb3X95z66lyEXsFyx6xquScJV16UkdCT3JeezzSTAaya0gmYjidsNIu-nNLTHdR0G61fYPlXamf7Sc1Wy3e_zi8-QcB_tIwTKPv75cJoW80O2Y_eQXtup8gW8dVAv1qTacB4VFW-_zGplZOcdH8Lb7arJW-ln-E-ul_jRtyrDP0A7ej8IbpbdZK8eISuethG9krPq4J03IiN4MLgEQQ0UGKR4_HXz9_xtJJSLa9_X07BcfDRB2zFp-F8rpf4pKqthoyGj_VPgJGlnTAvwNEWCo831dZ9iRc5Hk2GQe-tO_TdIYJPvf5gwLHIM3w0OXE3Lh-j2fDw22Dk1Y0XPBVRuvZkyKjg2qdExYLLxPbnyKzQjgohpQrFRZBoxojIAhUqSjSwDhIrFRJtAhXo8AnazYtcP0WYAzygUSyAhovIN4mkIiZZYDTwKCk476A3zatPVa1KbptjLFNgJ9ZQ6W1DddDr7egflRrHP8b1rRW3Y6yGtjtRrM7SOiRTYhLBTAKzAOIYyiURBtgW8eFnUaWSDjpofCBt_DIFhEhDAhkk7KCX28sQknafBcxUbNwYZtm-D7eIW77T-kLtK_li7sS9AbAmgOGe_f_hz9E9Yotr_Ngj8QHaXa82-gWgo7Xsor3-4WR63HX_LnRdGNwA1G8QtQ |
| linkProvider | Scholars Portal |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELbKVgguiKfYUsBI9ARREztOHKQK7W67ytJuWPUhlVOwHae70iopm11Qb_wIjvwWfgy_hHEeS3OAW09RYsd5zPibGWfyDUKvAe48w1puScKV5SaEWpLb0rI97UkHUFOWBKbjyAvP3A_n7HwD_Wr-hTFplQ0mlkCd5Mqske-CaWaUwNSl7y-_WKZqlPm62pTQEHVphWSvpBirf-w41FffIIQr9kb7IO8dQoYHp4PQqqsMWMplbGlJ6jHBtc2I8gWXgSlGkRhWGUXBfgjFhRNozyMicRRVjGhwsYmvFCU6dZSjKYx7C226ZgGlgzb7B9HkeL3KAwbe8bhbZdxTGti781mqTeo9mGrWsoVlyYCWn9vO0rxm9ob30b3aX8W9SsEeoA2dPUS3qwqWV4_Qzx42iLLQ0yoRHjckJzhPcQhAAqG4yPD44_4nPKkoXIvf339MQGHx6B02pNdwPNNzfFLldIMlxcf6K7ivhTlhmoOCzxQer6qUgQLPMhxGQ6f3ttz0y40Le73-YMCxyBI8ik7KgYvH6OxGRPEEdbI8008R5uCWMNcXEP4L104DyYRPEifVEL9JwXkXvWlefaxqNnRTlGMeQ1RkBBVfF1QX7ax7X1YsIP_o1zdSXPcx3N3lgXxxEddQEJM0EF4awFngWqWMSyJSiPKIDY_FlAq6aLvRgbgGlCL-q_5d9GrdDFBgvu-AmPJV2cczqww2DOG3dKd1Q-2WbDYtScXBUQ7Ad9z6_8Vfojvh6fgoPhpFh8_QXWISfGzfIv426iwXK_0cPLSlfFFPA4w-3_TM-wMEyk9q |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3NbtNAEF6VViAuiF8RKLBI9ARW7LV3vUaqUH4aJZSEqKVSOZnd9S6JFNklTkC98RAceSIeo0_SWf-E-gC3nizb63XimflmZj3-BqFXAHfMspY7knDlBAnxHcld6bhMM-kBasqCwHQ8YcOT4P0pPd1Cf-pvYWxZZY2JBVAnmbJr5G1wzdQnYLp-21RlEdP-4N3ZN8d2kLJvWut2GqJqs5DsF3Rj1Uceh_r8B6Rz-f6oD7LfI2Rw8Kk3dKqOA44KKF050mdUcO1SokLBZWQbUySWYUb54EuE4sKLNGNEJJ7yFSUawm0SKuUTbTzlaR_mvYF2QvD6kAjudA8m06PNig84e4_xoKy-9_3IbS_mRtsyfHDbtOEXi_YBjZi3WbF5xQUO7qI7VeyKO6Wy3UNbOr2PbpbdLM8foN8dbNFlqWdlUTyuCU9wZvAQQAXScpHi8cf-Zzwt6Vzzi5-_pqC8ePQWWwJsOJ7qBT4u67vBq-Ij_R1C2dxeMMtA2ecKj9dl-UCO5ykeTgZe502x6RabAPY63V6PY5EmeDQ5LibOH6KTaxHFI7SdZql-jDCHEIUGoXADJgLXRJKKkCSe0ZDLScF5C72uH32sKmZ026BjEUOGZAUVXxVUC-1tRp-VjCD_GNe1UtyMsTzexYFs-TWuYCEmJhLMRHAVhFmGckmEgYyPuPC3qFJRC-3WOhBX4JLHf02hhV5uTgMs2Hc9IKZsXYxhdsXBhSnChu40flDzTDqfFQTjEDRHEEc--f_NX6BbYIHxh9Hk8Cm6TWytjxs6JNxF26vlWj-DYG0ln1dWgNGX6za8S7joU64 |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Comprehensive+Analysis+of+Hungarian+MODY+Patients%E2%80%94Part+I%3A+Gene+Panel+Sequencing+Reveals+Pathogenic+Mutations+in+HNF1A%2C+HNF1B%2C+HNF4A%2C+ABCC8+and+INS+Genes&rft.jtitle=Life+%28Basel%2C+Switzerland%29&rft.au=Ga%C3%A1l%2C+Zsolt&rft.au=Sz%C5%B1cs%2C+Zsuzsanna&rft.au=K%C3%A1ntor%2C+Ir%C3%A9n&rft.au=Luczay%2C+Andrea&rft.date=2021-07-27&rft.pub=MDPI+AG&rft.eissn=2075-1729&rft.volume=11&rft.issue=8&rft.spage=755&rft_id=info:doi/10.3390%2Flife11080755&rft.externalDBID=HAS_PDF_LINK |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2075-1729&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2075-1729&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2075-1729&client=summon |