A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency

Taku Nakagawa, Mariko Ikeda, Yoshiko Murakami, Shota Nakamura, Daisuke Motooka, Tomomi Emoto, Wataru Satake, Masahiro Nishiyama, Daisaku Toyoshima, Naoya Morisada, Satoshi Takada, Shinya Tairaku, Nobuhiko Okamoto, Ichiro Morioka, Hiroki Kurahashi, Tatsushi Toda, Taroh Kinoshita, Kazumoto Iijima

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic pathway cause inherited GPI deficiencies (IGDs) characterized by multiple congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and epilepsy. We report the case of a 6-year-old boy with severe psychomotor developmental delay, epilepsy, and decreased granulocyte surface expression of GPI-anchored protein that suggested autosomal recessive GPI deficiency. The case underwent target exome sequencing to screen for IGDs. Target exome sequencing of the proband identified an apparently homozygous c.808T>C (p.Ser270Pro) mutation in PIGN, a gene involved in the GPI anchor biosynthetic pathway. As his parents were expecting another child, genetic carrier screening was conducted for the parents. Direct sequencing of the parents identified a heterozygous c.808T>C PIGN mutation in the father but none in the mother. To identify the mother's mutation, we performed semi-quantitative real-time PCR of the PIGN exons and long PCR, identifying a microdeletion in PIGN (del exons 2-14). The proband had inherited this microdeletion from his mother. Prenatal diagnosis of the fetus revealed that it was a heterozygous carrier of the mother's pathogenic allele. Here, we report a sporadic case of inherited GPI deficiency with a PIGN mutation and the first case of prenatal diagnosis for GPI deficiency.

Original languageEnglish
Pages (from-to)183-188
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume170
Issue number1
DOIs
Publication statusPublished - 01-01-2016

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Glycosylphosphatidylinositols
Prenatal Diagnosis
Mothers
Exome
Mutation
Parents
Biosynthetic Pathways
Exons
Epilepsy
Muscle Hypotonia
Genetic Testing
Heterozygote
Granulocytes
Fathers
Real-Time Polymerase Chain Reaction
Proteins
Fetus
Alleles
Cell Membrane
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Nakagawa, Taku ; Ikeda, Mariko ; Murakami, Yoshiko ; Nakamura, Shota ; Motooka, Daisuke ; Emoto, Tomomi ; Satake, Wataru ; Nishiyama, Masahiro ; Toyoshima, Daisaku ; Morisada, Naoya ; Takada, Satoshi ; Tairaku, Shinya ; Okamoto, Nobuhiko ; Morioka, Ichiro ; Kurahashi, Hiroki ; Toda, Tatsushi ; Kinoshita, Taroh ; Iijima, Kazumoto. / A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency. In: American Journal of Medical Genetics, Part A. 2016 ; Vol. 170, No. 1. pp. 183-188.
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Nakagawa, T, Ikeda, M, Murakami, Y, Nakamura, S, Motooka, D, Emoto, T, Satake, W, Nishiyama, M, Toyoshima, D, Morisada, N, Takada, S, Tairaku, S, Okamoto, N, Morioka, I, Kurahashi, H, Toda, T, Kinoshita, T & Iijima, K 2016, 'A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency', American Journal of Medical Genetics, Part A, vol. 170, no. 1, pp. 183-188. https://doi.org/10.1002/ajmg.a.37397

A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency. / Nakagawa, Taku; Ikeda, Mariko; Murakami, Yoshiko; Nakamura, Shota; Motooka, Daisuke; Emoto, Tomomi; Satake, Wataru; Nishiyama, Masahiro; Toyoshima, Daisaku; Morisada, Naoya; Takada, Satoshi; Tairaku, Shinya; Okamoto, Nobuhiko; Morioka, Ichiro; Kurahashi, Hiroki; Toda, Tatsushi; Kinoshita, Taroh; Iijima, Kazumoto.

In: American Journal of Medical Genetics, Part A, Vol. 170, No. 1, 01.01.2016, p. 183-188.

Research output: Contribution to journalArticle

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T1 - A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency

AU - Nakagawa, Taku

AU - Ikeda, Mariko

AU - Murakami, Yoshiko

AU - Nakamura, Shota

AU - Motooka, Daisuke

AU - Emoto, Tomomi

AU - Satake, Wataru

AU - Nishiyama, Masahiro

AU - Toyoshima, Daisaku

AU - Morisada, Naoya

AU - Takada, Satoshi

AU - Tairaku, Shinya

AU - Okamoto, Nobuhiko

AU - Morioka, Ichiro

AU - Kurahashi, Hiroki

AU - Toda, Tatsushi

AU - Kinoshita, Taroh

AU - Iijima, Kazumoto

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N2 - Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic pathway cause inherited GPI deficiencies (IGDs) characterized by multiple congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and epilepsy. We report the case of a 6-year-old boy with severe psychomotor developmental delay, epilepsy, and decreased granulocyte surface expression of GPI-anchored protein that suggested autosomal recessive GPI deficiency. The case underwent target exome sequencing to screen for IGDs. Target exome sequencing of the proband identified an apparently homozygous c.808T>C (p.Ser270Pro) mutation in PIGN, a gene involved in the GPI anchor biosynthetic pathway. As his parents were expecting another child, genetic carrier screening was conducted for the parents. Direct sequencing of the parents identified a heterozygous c.808T>C PIGN mutation in the father but none in the mother. To identify the mother's mutation, we performed semi-quantitative real-time PCR of the PIGN exons and long PCR, identifying a microdeletion in PIGN (del exons 2-14). The proband had inherited this microdeletion from his mother. Prenatal diagnosis of the fetus revealed that it was a heterozygous carrier of the mother's pathogenic allele. Here, we report a sporadic case of inherited GPI deficiency with a PIGN mutation and the first case of prenatal diagnosis for GPI deficiency.

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