Genetic variations in the GLUT3 gene associated with myelomeningocele.

Our objectives were to examine the extent of described sequence variation in the glucose transporter 3 (GLUT3) gene in children with myelomeningocele (MM), identify novel variations in the GLUT3 gene in these children, and determine whether these variations may confer a risk of MM. We sequenced the 10 exons of GLUT3, including exon-intron boundaries, on 96 children with MM. Sequencing was performed with Sanger methods and results analyzed with deoxyribonucleic acid analysis software. Frequencies of known single-nucleotide polymorphisms were identified, and those differing from the reference sequence (GRCh37/hg19 assembly) were considered variations. Six novel and 9 previously described, genetic variations were identified in our population. The novel variations included a large, 83 base pair deletion involving the core promoter region and part of exon 1 (1 of 96 children), and a 2 base pair deletion in the coding sequence of exon 4 (1 of 96 children). The remaining novel variations were located in the introns in the proximity of the splice sites. Novel mutations in GLUT3 were observed among 6.25% of our population. Additionally, the frequency of the rare allele for rs17847972 located in a splice donor site is higher (P < .001) in MM in our population than expected. We identified previously undescribed deletions and single-nucleotide variations involving the GLUT3 gene that may be associated with increased susceptibility to MM. Of particular interest, the 2 deletions involve both an important core promoter site and a coding region predicted to have a deleterious effect. The functional significance of these findings is under investigation.