Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency
| Autor: | Yukina Nishito, Yoshie Kibihara, Hiroshi Narita, Riko Ishida, Kazuhisa Fukue, Risa Tamagawa-Mineoka, Taiho Kambe, Naoya Itsumura, Akiko Miyata, Hiroko Kodama, Norito Katoh, Kenji Fukushima |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Heterozygote Mutant Mutation Missense Mothers Single-nucleotide polymorphism Biology medicine.disease_cause Polymorphism Single Nucleotide 03 medical and health sciences Japan medicine Missense mutation Humans Genetic Predisposition to Disease Cation Transport Proteins Growth Disorders Genetics Mutation 030102 biochemistry & molecular biology Milk Human Infant Newborn Infant Heterozygote advantage Biological Transport Sequence Analysis DNA medicine.disease Solute carrier family Alternative Splicing Zinc 030104 developmental biology Breast Feeding Phenotype Pediatrics Perinatology and Child Health Zinc deficiency Female Breast feeding |
| Zdroj: | Pediatric research. 80(4) |
| ISSN: | 1530-0447 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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