短暂性新生儿锌缺乏症发病机制中的新突变
Novel mutations in the pathogenesis of transient neonatal zinc deficiency.
作者信息
Muto Taichiro, Kawase Yuriko, Aiba Kaori, Okuma Miyuki, Itsumura Naoya, Luo Shuangyu, Ogawa Namino, Tsuji Tokuji, Kambe Taiho
机构信息
Department of Pediatrics Aichi Medical University Hospital Nagakute Japan.
Department of Dermatology Toshiba Central Hospital Tokyo Japan.
出版信息
Pediatr Investig. 2023 Feb 22;7(1):6-12. doi: 10.1002/ped4.12366. eCollection 2023 Mar.
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 () 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
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 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 promoter, the first mutations in the regulatory region reported to date.
INTERPRETATION
This report provides new genetic insights into TNZD pathogenesis in breastfed infants.
重要性
由于母乳中锌水平异常低，母乳喂养的婴儿会出现短暂性新生儿锌缺乏（TNZD）。编码锌转运蛋白ZNT2的溶质载体家族30成员2（）基因突变会导致母乳中锌浓度降低。
目的
本研究旨在进一步深入了解TNZD的病理生理学。
方法
对三名不相关的日本母亲进行测序，她们的婴儿因食用低锌牛奶而患上TNZD。使用基于细胞的检测方法和荧光素酶报告基因分析来检测所鉴定突变的影响。
结果
在每位母亲中都鉴定出了新的突变。其中一位母亲在ZNT2锌结合位点存在杂合错义突变，导致锌转运缺陷。另外两位母亲在启动子中出现多个杂合突变，这是迄今为止报道的调控区域中的首次突变。
解读
本报告为母乳喂养婴儿TNZD的发病机制提供了新的遗传学见解。
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