Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption

Daniel Sanghoon Shin, Kris Mahadeo, Sang Hee Min, Ndeye Diop-Bove, Peter Clayton, Rongbao Zhao, I. David Goldman

Research output: Contribution to journalArticle

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalMolecular Genetics and Metabolism
Issue number1
Publication statusPublished - May 1 2011



  • Folates, proton-coupled transport
  • HFM, hereditary folate malabsorption
  • Heme carrier protein 1
  • Intestinal folate transport
  • PCFT, proton-coupled folate transporter

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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