Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency

• 神戸, 大朋

• Kibihara, Yoshie

• Fukue, Kazuhisa

• Miyata, Akiko

• Fukushima, Kenji

• Tamagawa-Mineoka, Risa

• Katoh, Norito

• Nishito, Yukina

• Ishida, Riko

• Narita, Hiroshi

• Kodama, Hiroko

• Kambe, Taiho

抄録

BACKGROUND: Infants are vulnerable to zinc deficiency. Thus, abnormally low breast milk zinc levels cause transient neonatal zinc deficiency (TNZD) in breast-fed infants. TNZD has been considered to be rare because of a paucity of citations in the published literature. However, recent studies of affected mothers identified four missense mutations in the solute carrier family 30 member 2 gene (SLC30A2), which encodes the zinc transporter, ZnT2. METHODS: Genetic analyses of SLC30A2/ZnT2 in three Japanese mothers secreting low-zinc milk (whose infants developed TNZD) were performed. The effects of identified mutations were examined in a cell-based assay. Furthermore, 31 single-nucleotide polymorphisms (SNPs) in SLC30A2/ZnT2 were evaluated for their potential involvement in low-zinc levels in milk. RESULTS: Each mother had a different novel heterozygous mutation in SLC30A2/ZnT2. One mutation reduced splicing efficiency of the SLC30A2/ZnT2 transcript, and all ZnT2 mutants were defective in zinc transport and were unstable in cells. Moreover, four SNPs caused a significant loss of zinc-transport activity, similar to that in disease-causing ZnT2 mutants. CONCLUSION: Our results indicate that many SLC30A2/ZnT2 mutations cause or potentially cause TNZD. Genetic information concerning TNZD pathogenesis is limited, and our results suggest that the TNZD frequency may be higher than previously thought.

収録刊行物

• Pediatric Research

  Pediatric Research 80 (4), 586-594, 2016-10

  Springer Nature

詳細情報

• CRID: 1050566774769988480
• NII論文ID: 120006863495
• ISSN: 00313998
• HANDLE: 2433/252308
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles
  • KAKEN