Open AccessHigh proportion of transient neonatal zinc deficiency causing alleles in the general population
Author(s) -
Golan Yarden,
Lehvy Adrian,
Horev Guy,
Assaraf Yehuda G.
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13982
Subject(s) - missense mutation , allele , biology , genetics , population , allele frequency , mutation , compound heterozygosity , newborn screening , gene , medicine , environmental health
Loss of function (LoF) mutations in the zinc transporter SLC 30A2/ZnT2 result in impaired zinc secretion into breast milk consequently causing transient neonatal zinc deficiency ( TNZD ) in exclusively breastfed infants. However, the frequency of TNZD causing alleles in the general population is yet unknown. Herein, we investigated 115 missense SLC 30A2/ZnT2 mutations from the Ex AC database, equally distributed in the entire coding region, harboured in 668 alleles in 60 706 healthy individuals of diverse ethnicity. To estimate the frequency of LoF SLC 30A2/ZnT2 mutations in the general population, we used bioinformatics tools to predict the potential impact of these mutations on ZnT2 functionality, and corroborated these predictions by a zinc transport assay in human MCF ‐7 cells. We found 14 missense mutations that were markedly deleterious to zinc transport. Together with two conspicuous LoF mutations in the Ex AC database, 26 SLC 30A2/ZnT2 alleles harboured deleterious mutations, suggesting that at least 1 in 2334 newborn infants are at risk to develop TNZD . This high frequency of TNZD mutations combined with the World Health Organization‐promoted increase in the rate of exclusive breastfeeding highlights the importance of genetic screening for inactivating SLC 30A2/ZnT2 mutations in the general population for the early diagnosis and prevention of TNZD .