New insights on folic add and neural tube defects: froe gene conversion events as increased risk

V. Capra, P. De Marco, A. Moroni, R. De Franchis, G. Andria, A. Cama

Research output: Contribution to journalArticle

Abstract

Periconceptional supplementation of folic add during pregnancy reduces up to 70% the risk of having children affected by neural tube defects. Receptors (FRs) mediate folate binding and cell internalization. They are encoded by three functional loci (a, β, y) and a pseudogene in tandem orientation on chromosome Ilql3. We have just showed in a subset of NTDs familiar cases, the presence of FRoe hybrid exons 6, comprising the terminal fragment of FRa gene and the remaining sequence of its pseudo-gene. These chimeric exons could be a consequence of mitotic unequal cross-over exchanges. Here we report the identification in three other unrelated patients of missense mutations in FRa exon 0. These deleterious substitutions, also found in normal individuals, were copied from a highly homologous pseudogene sequence and introduced in a KKa gene by a small-scale gene conversion mech;mism; since only few peripherical lymphocytes showed these genetic variants, we suggest that FRa gene conversion events involve somatic and not germinal cells. We hypothesize that both mechanisms, mitotic unequal crossover and small-scale gene conversion of FHa genes, could impair receptor function and the amount of involved receptors could be correlated to an increased risk of neural tube defect with a threshold effect for the population. For the first time, these results seem to give a genetic support to well-known epidemiological information.

Original languageEnglish
Pages (from-to)14
Number of pages1
JournalEuropean Journal of Pediatric Surgery, Supplement
Volume9
Issue number1
Publication statusPublished - 1999

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Gene Conversion
Neural Tube Defects
Exons
Pseudogenes
Genes
Missense Mutation
Sequence Homology
Folic Acid
Chromosomes
Lymphocytes
Pregnancy
Population

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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New insights on folic add and neural tube defects : froe gene conversion events as increased risk. / Capra, V.; De Marco, P.; Moroni, A.; De Franchis, R.; Andria, G.; Cama, A.

In: European Journal of Pediatric Surgery, Supplement, Vol. 9, No. 1, 1999, p. 14.

Research output: Contribution to journalArticle

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