Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency

Winyoo Chowanadisai, Bo Lönnerdal, Shannon L. Kelleher

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229 Scopus citations


Breast milk normally contains adequate zinc to meet infant requirements up to six months of age; however, transient neonatal zinc deficiency has been documented in exclusively breastfed infants of women with low milk zinc concentration. This condition is not corrected by maternal zinc supplementation, supporting the speculation that it results from an inherited genetic condition. We identified a family in which two exclusively breast-fed infants developed zinc deficiency that was associated with low milk zinc concentration in both women. Sequencing of genomic DNA detected a mis-sense mutation (Ade→Gua) that substitutes a conserved histidine at amino acid 54 with arginine (H54R) in SLC30A2 (ZnT-2) that is present in both affected subjects and several other siblings. Gene knock-down of SLC30A2 in mammary epithelial cells reduced zinc secretion, illustrating the role of ZnT-2 in zinc secretion from this cell type. Expression of the H54R mutant in human embryonic kidney-293 cells resulted in reduced zinc secretion as a consequence of perinuclear, aggresomal accumulation, whereas co-expression of the H54R mutant and wild-type ZnT-2 did not abrogate increased zinc secretion in cells overexpressing wild-type ZnT-2 alone. Together, these data provide evidence that low milk zinc concentration in some women is a consequence of a genetic disorder resulting from a mutation in SLC30A2 and can result in neonatal zinc deficiency if unrecognized. Further studies are needed to evaluate the incidence and penetrance of this mutation in the human population.

Original languageEnglish (US)
Pages (from-to)39699-39707
Number of pages9
JournalJournal of Biological Chemistry
Issue number51
StatePublished - Dec 22 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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