2. Academic Validation
  3. Phenotype-genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties

Phenotype-genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties

  • Hum Mutat. 2017 Jul;38(7):805-815. doi: 10.1002/humu.23219.
Junpei Tanigawa 1,  Haruka Mimatsu 2,  Seiji Mizuno 3,  Nobuhiko Okamoto 4,  Daisuke Fukushi 5,  Koji Tominaga 1 6,  Hiroyuki Kidokoro 7,  Yukako Muramatsu 2,  Eriko Nishi 3,  Shota Nakamura 8,  Daisuke Motooka 8,  Noriko Nomura 5,  Kiyoshi Hayasaka 9,  Tetsuya Niihori 10,  Yoko Aoki 10,  Shin Nabatame 1,  Masahiro Hayakawa 2,  Jun Natsume 11,  Keiichi Ozono 1,  Taroh Kinoshita 12,  Nobuaki Wakamatsu 5,  Yoshiko Murakami 12
Affiliations

Affiliations

  • 1 Department of Pediatrics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • 2 Division of Neonatology Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Aichi, Japan.
  • 3 Department of Pediatrics, Central Hospital, Aichi Human Service Center, Kasugai, Aichi, Japan.
  • 4 Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan.
  • 5 Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
  • 6 Department of Child Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
  • 7 Department of Pediatrics, Nagoya University Hospital, Nagoya, Aichi, Japan.
  • 8 Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
  • 9 Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Yamagata, Japan.
  • 10 Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
  • 11 Department of Developmental Disability Medicine and Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • 12 Department of Immunoregulation, Research Institute for Microbial Diseases Osaka University, Suita, Osaka, Japan.
PMID: 28337824 DOI: 10.1002/humu.23219
Abstract

Inherited GPI (glycosylphosphatidylinositol) deficiencies (IGDs), a recently defined group of diseases, show a broad spectrum of symptoms. Hyperphosphatasia mental retardation syndrome, also known as Mabry syndrome, is a type of IGDs. There are at least 26 genes involved in the biosynthesis and transport of GPI-anchored proteins; however, IGDs constitute a rare group of diseases, and correlations between the spectrum of symptoms and affected genes or the type of mutations have not been shown. Here, we report four newly identified and five previously described Japanese families with PIGO (phosphatidylinositol glycan anchor biosynthesis class O) deficiency. We show how the clinical severity of IGDs correlates with flow cytometric analysis of blood, functional analysis using a PIGO-deficient cell line, and the degree of hyperphosphatasia. The flow cytometric analysis and hyperphosphatasia are useful for IGD diagnosis, but the expression level of GPI-anchored proteins and the degree of hyperphosphatasia do not correlate, although functional studies do, with clinical severity. Compared with PIGA (phosphatidylinositol glycan anchor biosynthesis class A) deficiency, PIGO deficiency shows characteristic features, such as Hirschsprung disease, brachytelephalangy, and hyperphosphatasia. This report shows the precise spectrum of symptoms according to the severity of mutations and compares symptoms between different types of IGD.

Keywords

Hirschsprung disease; PIGO; epilepsy; glycosylphosphatidylinositol (GPI); inherited glycosylphosphatidylinositol deficiency (IGD).

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