Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency.
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.
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
Naoya
N
Itsumura
Department of Food Science, Kyoto Women's University, Kyoto, Japan.
Yoshie
Y
Kibihara
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
Kazuhisa
K
Fukue
Saiwai Pediatric Clinic, Tokyo, Japan.
Akiko
A
Miyata
Department of Pediatrics, San-in Rosai Hospital, Yonago, Japan.|Current affiliation: Department of Pediatrics, Tottori University Hospital, Yonago, Japan.
Kenji
K
Fukushima
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Risa
R
Tamagawa-Mineoka
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Norito
N
Katoh
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
Yukina
Y
Nishito
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
Riko
R
Ishida
Department of Food Science, Kyoto Women's University, Kyoto, Japan.
Hiroshi
H
Narita
Department of Pediatrics, School of Medicine, Teikyo University, Tokyo, Japan.|Department of Health and Dietetics, Faculty of Health and Medical Sciences, Teikyo Heisei University, Tokyo, Japan.
Hiroko
H
Kodama
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
Taiho
0000-0001-9757-063X
T
Kambe
D017398:Alternative Splicing; D001692:Biological Transport; D001942:Breast Feeding; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D009035:Mothers; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D015032:Zinc / Q000737:chemistry / Q000172:deficiency*
D027682:Cation Transport Proteins; C486299:SLC30A2 protein, human; D015032:Zinc