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...

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Bibliographic Details
Published in:Pediatric investigation 2023-03, Vol.7 (1), p.6-12
Main Authors: Muto, Taichiro, Kawase, Yuriko, Aiba, Kaori, Okuma, Miyuki, Itsumura, Naoya, Luo, Shuangyu, Ogawa, Namino, Tsuji, Tokuji, Kambe, Taiho
Format: Article
Language:English
Subjects:
Breastfeeding
Breastfeeding & lactation
Dermatitis
Dermatology
Families & family life
Low‐zinc breast milk
Mutation
Newborn babies
Original
Pathogenesis
Promoter
Proteins
SLC30A2/ZNT2
Steroids
Transient neonatal zinc deficiency (TNZD)
Vitamin deficiency
Weaning
Zinc
Zinc‐binding motif
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Summary: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. Two novel heterozygous SLC30A2/ZNT2 mutations were identified from mothers whose infants suffered from TNZD. The first is a loss‐of‐function mutation, which changed the intramembranous HDHD zinc‐binding motif to an HDHN motif, resulting in zinc transport activity loss. The other involves multiple mutations identified for the first time in the SLC30A2/ZNT2 promoter region.
ISSN:2574-2272
2096-3726
2574-2272
DOI:10.1002/ped4.12366