title: Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption.
abstract: Hereditary folate malabsorption (HFM) is an autosomal recessive disorder, recently shown to be due to loss-of-function mutations of the proton-coupled folate transporter (PCFT-SLC46A1), resulting in systemic and central nervous system folate deficiency. Data is emerging on the spectrum of PCFT mutations associated with this disorder. In this report, novel mutations are described in three subjects with HFM: A335D/N68Kfs (c.1004C>A/c.204-205delCC), compound heterozygous mutations, and two homozygous PCFT mutations, G338R (c.1012G>C) and E9Gfs (c.17-18insC). Functional assessment of A335D and G338R PCFT mutants transfected into folate transporter-deficient HeLa R1-11 cells indicated a complete loss of transport activity. There were neurological deficiencies in two of the families reported; in particular, late-onset seizures. The importance of early diagnosis and treatment to achieve physiological cerebrospinal fluid folate levels is emphasized.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Daniel Sanghoon
authors.initials: DS
authors.lastname: Shin
authors.forename: Kris
authors.initials: K
authors.lastname: Mahadeo
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Min
authors.forename: Ndeye
authors.initials: N
authors.lastname: Diop-Bove
authors.forename: Peter
authors.initials: P
authors.lastname: Clayton
authors.forename: Rongbao
authors.initials: R
authors.lastname: Zhao
authors.forename: I David
authors.initials: ID
authors.lastname: Goldman
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D056726:Genetic Association Studies; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D008286:Malabsorption Syndromes / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D058979:Proton-Coupled Folate Transporter / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D058979:Proton-Coupled Folate Transporter