Itsumura Naoya, Kibihara Yoshie, Fukue Kazuhisa, Miyata Akiko, Fukushima Kenji, Tamagawa-Mineoka Risa, Katoh Norito, Nishito Yukina, Ishida Riko, Narita Hiroshi, Kodama Hiroko, Kambe Taiho
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
Department of Food Science, Kyoto Women's University, Kyoto, Japan.
Pediatr Res. 2016 Oct;80(4):586-94. doi: 10.1038/pr.2016.108. Epub 2016 May 16.
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.
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.
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.
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.
婴儿易患锌缺乏症。因此，母乳中锌水平异常低下会导致母乳喂养的婴儿出现短暂性新生儿锌缺乏症（TNZD）。由于已发表文献中相关引用较少，TNZD一直被认为较为罕见。然而，最近对受影响母亲的研究在溶质载体家族30成员2基因（SLC30A2）中发现了四个错义突变，该基因编码锌转运蛋白ZnT2。
对三名分泌低锌母乳（其婴儿患TNZD）的日本母亲的SLC30A2/ZnT2进行了基因分析。在细胞实验中检测了所发现突变的影响。此外，还评估了SLC30A2/ZnT2中的31个单核苷酸多态性（SNP）与母乳低锌水平的潜在关联。
每位母亲的SLC30A2/ZnT2都有一个不同的新型杂合突变。一个突变降低了SLC30A2/ZnT2转录本的剪接效率，所有ZnT2突变体在锌转运方面存在缺陷且在细胞中不稳定。此外，四个SNP导致锌转运活性显著丧失，类似于致病的ZnT2突变体。
我们的结果表明，许多SLC30A2/ZnT2突变会导致或可能导致TNZD。关于TNZD发病机制的遗传信息有限，我们的结果表明TNZD的发生率可能高于先前的认识。
