title: A novel PCFT gene mutation (p.Cys66LeufsX99) causing hereditary folate malabsorption.
abstract: Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder which is characterized by impaired intestinal folate malabsorption and impaired folate transport into the central nervous system. Mutations in the intestinal folate transporter PCFT have been reported previously in only 10 individuals with this disorder. The purpose of the current study was to describe the clinical phenotype and determine the molecular basis for this disorder in a family with four affected individuals. A consanguineous family of Pakistani origin with autosomal recessive HFM was ascertained and clinically phenotyped. After genetic linkage studies all coding exons of the PCFT gene were screened for mutations by direct sequencing. The clinical phenotype of four affected patients is described. Direct sequencing of PCFT revealed a novel homozygous frameshift mutation (c.194dupG) at a mononucleotide repeat in exon 1 predicted to result in a truncated protein (p.Cys66LeufsX99). This report extends current knowledge on the phenotypic manifestations of HFM and the PCFT mutation spectrum.
authors.affiliation: Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK. e.meyer@bham.ac.uk
authors.forename: Esther
authors.initials: E
authors.lastname: Meyer
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.forename: Shanaz
authors.initials: S
authors.lastname: Pasha
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000328:Adult; D002648:Child; D003241:Consanguinity; D005190:Family; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D016368:Frameshift Mutation; D006801:Humans; D007408:Intestinal Absorption / Q000235:genetics; D008286:Malabsorption Syndromes / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D010641:Phenotype; D058979:Proton-Coupled Folate Transporter
chemical_list: D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; C505058:SLC46A1 protein, human; D005492:Folic Acid