Transient Neonatal Zinc Deficiency Caused by a Heterozygous G87R Mutation in theZinc Transporter ZnT-2 (SLC30A2)Gene in the Mother Highlighting the Importance of Zn²⁺for Normal Growth and Development

Abstract

Suboptimal dietary zinc (Zn2+) intake is increasingly appreciated as an important public health issue. Zn2+ is an essential mineral, and infants are particularly vulnerable to Zn2+ deficiency, as they require large amounts of Zn2+ for their normal growth and development. Although term infants are born with an important hepatic Zn2+ storage, adequate Zn2+ nutrition of infants mostly depends on breast milk or formula feeding, which contains an adequate amount of Zn2+ to meet the infants' requirements. An exclusively breast-fed 6 months old infant suffering from Zn2+ deficiency caused by an autosomal dominant negative G87R mutation in the Slc30a2 gene (encoding for the zinc transporter 2 (ZnT-2)) in the mother is reported. More than 20 zinc transporters characterized up to date, classified into two families (Slc30a/ZnT and Slc39a/Zip), reflect the complexity and importance of maintaining cellular Zn2+ homeostasis and dynamics. The role of ZnTs is to reduce intracellular Zn2+ by transporting it from the cytoplasm into various intracellular organelles and by moving Zn2+ into extracellular space. Zips increase intracellular Zn2+ by transporting it in the opposite direction. Thus the coordinated action of both is essential for the maintenance of Zn2+ homeostasis in the cytoplasm, and accumulating evidence suggests that this is also true for the secretory pathway of growth hormone.

Exome Sequencing of SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants Associated with Breast Cell Dysfunction

“…In humans, four missense mutations identified in SLC30A2 are Electronic supplementary material The online version of this article (doi:10.1007/s10911-015-9338-z) contains supplementary material, which is available to authorized users. associated with a 50-90 % reduction in milk Zn concentration [Zn] [8][9][10][11], resulting in severe neonatal Zn deficiency in exclusively breastfed infants. Additionally, two single nucleotide polymorphisms (SNPs) in ZnT2 (rs35235055, L 23 P and rs35623192, R 340 C), are mis-localized and result in either loss (L 23 P) or gain (R 340 C) of Zn secretion capacity [12].…”

Differential expression of zinc transporters accompanies the differentiation of C2C12 myoblasts

“…ZnT2 expression is induced by elevated Zn levels, and has been detected in mammary glands, prostate, pancreas, small intestine, kidney, and retina [31,59,60]. ZnT2 is necessary for secretion of Zn into breast milk in humans [61–64]. ZnT3 is located mainly in synaptic vesicles of glutamatergic neurons located in the hippocampus, but is proposed to also modulate insulin production in pancreatic β cells [65–67].…”

Transient Neonatal Zinc Deficiency Caused by a Novel Mutation in the SLC30A2 Gene

“…Symptoms begin in affected infants after the first few months of life while they are exclusively breastfed. Seven variants have been reported: H54R (c.161A>G); G87R (c.259G>C), (c.1031A>G), (c.697T>C); W152R (c.454T>C); S296L (c.887>T); and F221fsX224 (663delC) (1)(2)(3)(4)(5). Genotype-phenotype correlation has not been determined because these various mutations are associated with different severities of zinc deficiency (1,2,5).…”