TY - JOUR
T1 - Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption
AU - Shin, Daniel Sanghoon
AU - Mahadeo, Kris
AU - Min, Sang Hee
AU - Diop-Bove, Ndeye
AU - Clayton, Peter
AU - Zhao, Rongbao
AU - Goldman, I. David
N1 - Funding Information:
The authors do not have competing financial interests. Professor Peter Clayton (Great Ormond Street Hospital for Children, London, UK) provided blood specimens and clinical information on patient 1. Dr. Clayton is funded by Great Ormond Street Children's Charity . We wish to thank Dr. Sami Jebnoun (Neonatology, Maternity and Neonatology Center, Tunis, Tunisia) for providing blood specimens and clinical information on patients 2 and 3 and Keris KrennHrubec for her invaluable assistance in transporting these specimens to our laboratory.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Folates, proton-coupled transport
KW - HCP1, PCFT/HCP1
KW - HFM, hereditary folate malabsorption
KW - Heme carrier protein 1
KW - Intestinal folate transport
KW - PCFT, proton-coupled folate transporter
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U2 - 10.1016/j.ymgme.2011.01.008
DO - 10.1016/j.ymgme.2011.01.008
M3 - Article
C2 - 21333572
AN - SCOPUS:79955149687
SN - 1096-7192
VL - 103
SP - 33
EP - 37
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
IS - 1
ER -
