Abstract
Alpha-fetoprotein (AFP) is the main fetus serum glycoprotein with a very low concentration in the adult. AFP deficiency is a rare phenomenon. We studied two families with congenital AFP deficiency and searched for mutations in the AFP gene. We identified one mutation of 2 base deletion in exon 8, in both families, that leads to the congenital deficiency of AFP. The mutation nt930-931delCT (T294fs25X) creates a frameshift after codon 294 that leads to a stop codon after 24 amino acids, thus truncating the normal length of AFP of 609 amino acids. All the affected children were found to be homozygous for the mutation as was one of the fathers. The affected individuals were asymptomatic and presented normal development. This first identification of a mutation in the AFP gene demonstrates for the first time that deficiency of AFP is compatible with human normal fetal development and further reproduction in males.
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Acknowledgements
We thank the members of the families for their cooperation in this study. We also thank Professor Rivka Carmi for a critical review of the manuscript, and the anonymous reviewers for their valuable suggestions. This project was sponsored in part by the Helen Tennen fund.
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GenBank,http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed (for human AFP mRNA NM_001134, for human AFP gene cluster NT_006216, for mouse AFP gene cluster NT_039308, for rat AFP gene cluster NW_047424).
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Sharony, R., Zadik, I. & Parvari, R. Congenital deficiency of alpha feto-protein. Eur J Hum Genet 12, 871–874 (2004). https://doi.org/10.1038/sj.ejhg.5201246
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DOI: https://doi.org/10.1038/sj.ejhg.5201246
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