2. Academic Validation
  3. A deep intronic mutation of c.1166-285 T > G in SLC46A1 is shared by four unrelated Japanese patients with hereditary folate malabsorption (HFM)

A deep intronic mutation of c.1166-285 T > G in SLC46A1 is shared by four unrelated Japanese patients with hereditary folate malabsorption (HFM)

  • Clin Immunol. 2019 Nov;208:108256. doi: 10.1016/j.clim.2019.108256.
Yusuke Tozawa 1,  Shimaa Said Mohamed Ali Abdrabou 1,  Natsuko Nogawa-Chida 2,  Ritsuo Nishiuchi 3,  Toshiaki Ishida 4,  Yuichi Suzuki 5,  Hideki Sano 6,  Ryoji Kobayashi 7,  Kenji Kishimoto 7,  Osamu Ohara 8,  Kohsuke Imai 9,  Takuya Naruto 10,  Kunihiko Kobayashi 7,  Tadashi Ariga 11,  Masafumi Yamada 12
Affiliations

Affiliations

  • 1 Department of Pediatrics, Division of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
  • 2 Department of Pediatrics, Division of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Department of Dentistry for Children and Disabled Persons, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.
  • 3 Department of Pediatrics, Kochi Health Sciences Centre, Kochi, Japan.
  • 4 Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
  • 5 Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan.
  • 6 Department of Pediatric Oncology, Fukushima Medical University Hospital, Fukushima, Japan.
  • 7 Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan.
  • 8 Department of Human Genome Technology, Kazusa DNA Research Institute, Chiba, Japan.
  • 9 Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • 10 Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
  • 11 Department of Pediatrics, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
  • 12 Department of Pediatrics, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: yamadam@med.hokudai.ac.jp.
PMID: 31494288 DOI: 10.1016/j.clim.2019.108256
Abstract

Hereditary folate malabsorption (HFM) is an autosomal recessive disease caused by mutations in SLC46A1 encoding the proton-coupled folate transporter (PCFT). HFM patients present with various clinical features including megaloblastic anemia, thrombocytopenia, combined immunodeficiency and neurodevelopmental disorders. In this study, we report the same deep intronic mutation of c.1166-285 T > G shared by four unrelated Japanese patients with HFM. This mutation was shown to generate a cryptic splice donor site for a 168-bp insertion of intron 3 sequences, leading to premature termination in the middle of this insertion. This mutation could be a founder mutation in the Japanese population, but also could be a hot-spot and could be present in undiagnosed HFM patients worldwide because of the difficulty to detect this mutation.

Keywords

Deep intronic mutation; Hereditary folate malabsorption (HFM); Megaloblastic anemia; Proton-coupled folate transporter (PCFT); SLC46A1.

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