Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency
ABSTRACT Importance Transient neonatal zinc deficiency (TNZD) occurs in breastfed infants due to abnormally low breast milk zinc levels. Mutations in the solute carrier family 30 member 2 (SLC30A2) gene, which encodes the zinc transporter ZNT2, cause low zinc concentration in breast milk. Objective...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-03-01
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| Series: | Pediatric Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ped4.12366 |
| _version_ | 1797866082787131392 |
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| author | Taichiro Muto Yuriko Kawase Kaori Aiba Miyuki Okuma Naoya Itsumura Shuangyu Luo Namino Ogawa Tokuji Tsuji Taiho Kambe |
| author_facet | Taichiro Muto Yuriko Kawase Kaori Aiba Miyuki Okuma Naoya Itsumura Shuangyu Luo Namino Ogawa Tokuji Tsuji Taiho Kambe |
| author_sort | Taichiro Muto |
| collection | DOAJ |
| description | ABSTRACT Importance Transient neonatal zinc deficiency (TNZD) occurs in breastfed infants due to abnormally low breast milk zinc levels. Mutations in the solute carrier family 30 member 2 (SLC30A2) gene, which encodes the zinc transporter ZNT2, cause low zinc concentration in breast milk. Objective This study aimed to provide further insights into TNZD pathophysiology. Methods SLC30A2 sequencing was performed in three unrelated Japanese mothers, whose infants developed TNZD due to low‐zinc milk consumption. The effects of the identified mutations were examined using cell‐based assays and luciferase reporter analysis. Results Novel SLC30A2 mutations were identified in each mother. One harbored a heterozygous missense mutation in the ZNT2 zinc‐binding site, which resulted in defective zinc transport. The other two mothers exhibited multiple heterozygous mutations in the SLC30A2 promoter, the first mutations in the SLC30A2 regulatory region reported to date. Interpretation This report provides new genetic insights into TNZD pathogenesis in breastfed infants. |
| first_indexed | 2024-04-09T23:18:21Z |
| format | Article |
| id | doaj.art-3c063150a0c64edc8fec9f6331a5588e |
| institution | Directory Open Access Journal |
| issn | 2574-2272 |
| language | English |
| last_indexed | 2024-04-09T23:18:21Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pediatric Investigation |
| spelling | doaj.art-3c063150a0c64edc8fec9f6331a5588e2023-03-22T04:45:12ZengWileyPediatric Investigation2574-22722023-03-017161210.1002/ped4.12366Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiencyTaichiro Muto0Yuriko Kawase1Kaori Aiba2Miyuki Okuma3Naoya Itsumura4Shuangyu Luo5Namino Ogawa6Tokuji Tsuji7Taiho Kambe8Department of Pediatrics Aichi Medical University Hospital Nagakute JapanDepartment of Dermatology Toshiba Central Hospital Tokyo JapanDepartment of Pediatrics Toyohashi Municipal Hospital Toyohashi JapanDepartment of Pediatrics Toshiba Central Hospital Tokyo JapanDepartment of Applied Molecular Biology, Division of Integrated Life Science Graduate School of Biostudies Kyoto University Kyoto JapanDepartment of Applied Molecular Biology, Division of Integrated Life Science Graduate School of Biostudies Kyoto University Kyoto JapanDepartment of Applied Molecular Biology, Division of Integrated Life Science Graduate School of Biostudies Kyoto University Kyoto JapanDepartment of Applied Molecular Biology, Division of Integrated Life Science Graduate School of Biostudies Kyoto University Kyoto JapanDepartment of Applied Molecular Biology, Division of Integrated Life Science Graduate School of Biostudies Kyoto University Kyoto JapanABSTRACT Importance Transient neonatal zinc deficiency (TNZD) occurs in breastfed infants due to abnormally low breast milk zinc levels. Mutations in the solute carrier family 30 member 2 (SLC30A2) gene, which encodes the zinc transporter ZNT2, cause low zinc concentration in breast milk. Objective This study aimed to provide further insights into TNZD pathophysiology. Methods SLC30A2 sequencing was performed in three unrelated Japanese mothers, whose infants developed TNZD due to low‐zinc milk consumption. The effects of the identified mutations were examined using cell‐based assays and luciferase reporter analysis. Results Novel SLC30A2 mutations were identified in each mother. One harbored a heterozygous missense mutation in the ZNT2 zinc‐binding site, which resulted in defective zinc transport. The other two mothers exhibited multiple heterozygous mutations in the SLC30A2 promoter, the first mutations in the SLC30A2 regulatory region reported to date. Interpretation This report provides new genetic insights into TNZD pathogenesis in breastfed infants.https://doi.org/10.1002/ped4.12366DermatologyBreastfeedingTransient neonatal zinc deficiency (TNZD)Low‐zinc breast milkSLC30A2/ZNT2Promoter |
| spellingShingle | Taichiro Muto Yuriko Kawase Kaori Aiba Miyuki Okuma Naoya Itsumura Shuangyu Luo Namino Ogawa Tokuji Tsuji Taiho Kambe Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency Pediatric Investigation Dermatology Breastfeeding Transient neonatal zinc deficiency (TNZD) Low‐zinc breast milk SLC30A2/ZNT2 Promoter |
| title | Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency |
| title_full | Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency |
| title_fullStr | Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency |
| title_full_unstemmed | Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency |
| title_short | Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency |
| title_sort | novel slc30a2 mutations in the pathogenesis of transient neonatal zinc deficiency |
| topic | Dermatology Breastfeeding Transient neonatal zinc deficiency (TNZD) Low‐zinc breast milk SLC30A2/ZNT2 Promoter |
| url | https://doi.org/10.1002/ped4.12366 |
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