Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young
Abstract Maturity-onset diabetes of the young type 4 (MODY4, PDX1-MODY) is a monogenic diabetes caused by the PDX1 gene. Here we detected two novel heterozygous missense variants, NM_000209.4(NP_000200.1):c.443G>T, p.(Arg148Leu) and c.442C>G p.(Arg148Gly), in two Japanese patients. Pathogenici...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-05-01
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| Series: | Human Genome Variation |
| Online Access: | https://doi.org/10.1038/s41439-025-00312-4 |
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| author | Satoshi Tanaka Hiroyuki Akagawa Michiyo Hase Naoko Iwasaki |
| author_facet | Satoshi Tanaka Hiroyuki Akagawa Michiyo Hase Naoko Iwasaki |
| author_sort | Satoshi Tanaka |
| collection | DOAJ |
| description | Abstract Maturity-onset diabetes of the young type 4 (MODY4, PDX1-MODY) is a monogenic diabetes caused by the PDX1 gene. Here we detected two novel heterozygous missense variants, NM_000209.4(NP_000200.1):c.443G>T, p.(Arg148Leu) and c.442C>G p.(Arg148Gly), in two Japanese patients. Pathogenicity testing revealed a loss of function in both variants. Family members had severe diabetic complications, including proliferative retinopathy and overt nephropathy such as end-stage renal disease. Laboratory testing indicated persistently high glucose levels, at least partially caused by reduced postprandial insulin secretion. |
| format | Article |
| id | doaj-art-a9bc5b1ce54e45ccbbaf398668839f21 |
| institution | DOAJ |
| issn | 2054-345X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Human Genome Variation |
| spelling | doaj-art-a9bc5b1ce54e45ccbbaf398668839f212025-08-20T03:10:20ZengNature Publishing GroupHuman Genome Variation2054-345X2025-05-011211410.1038/s41439-025-00312-4Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the youngSatoshi Tanaka0Hiroyuki Akagawa1Michiyo Hase2Naoko Iwasaki3Institute for Comprehensive Medical Sciences, Tokyo Women’s Medical UniversityInstitute for Comprehensive Medical Sciences, Tokyo Women’s Medical UniversityInstitute of Geriatrics, Tokyo Women’s Medical UniversityInstitute for Comprehensive Medical Sciences, Tokyo Women’s Medical UniversityAbstract Maturity-onset diabetes of the young type 4 (MODY4, PDX1-MODY) is a monogenic diabetes caused by the PDX1 gene. Here we detected two novel heterozygous missense variants, NM_000209.4(NP_000200.1):c.443G>T, p.(Arg148Leu) and c.442C>G p.(Arg148Gly), in two Japanese patients. Pathogenicity testing revealed a loss of function in both variants. Family members had severe diabetic complications, including proliferative retinopathy and overt nephropathy such as end-stage renal disease. Laboratory testing indicated persistently high glucose levels, at least partially caused by reduced postprandial insulin secretion.https://doi.org/10.1038/s41439-025-00312-4 |
| spellingShingle | Satoshi Tanaka Hiroyuki Akagawa Michiyo Hase Naoko Iwasaki Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young Human Genome Variation |
| title | Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young |
| title_full | Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young |
| title_fullStr | Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young |
| title_full_unstemmed | Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young |
| title_short | Two novel pathogenic PDX1 variants in two Japanese patients with maturity-onset diabetes of the young |
| title_sort | two novel pathogenic pdx1 variants in two japanese patients with maturity onset diabetes of the young |
| url | https://doi.org/10.1038/s41439-025-00312-4 |
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