Mutation of the proton-coupled folate transporter gene (PCFT-SLC46A1) in Turkish siblings with hereditary folate malabsorption

Abstract

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder characterized by systemic and central nervous system folate deficiency. Turkish siblings are reported with the clinical syndrome of HFM, homozygous for deletion of 2 bases (c.204_205 delCC) within the first exon of the proton-coupled folate transporter (PCFT) gene, causing a frameshift. Low blood and cerebrospinal fluid folate levels were detected at ages 3.5 and 1 month. Treatment with parenteral 5-formyltetrahydrofolate resulted in normal development now at ages 3 and 1 year. Extending current knowledge on the phenotypic manifestations of HFM and the PCFT mutation spectrum will provide opportunities to define possible genotype-phenotype correlations and clarify the basis for the phenotypic variability that is characteristic of this disorder.

FIGURE 1

(Top) Pedigree of the family. (Bottom) Chromatogram of the region in the first exon demonstrating deletion of 2 bases (CC, positions 300 and 301 based on NM_080669). The siblings are homozygous for this mutation. The mutated and wild-type alleles are detected in both parents, who are heterozygous.