title: A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency.
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.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.|Division of Genetic Counseling, Kobe University Hospital, Kobe, Japan.|Department of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Taniguchi-Ikeda
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.|Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Emoto
authors.affiliation: Department of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Satake
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Toyoshima
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Morisada
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takada
authors.affiliation: Division of Genetic Counseling, Kobe University Hospital, Kobe, Japan.|Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tairaku
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Morioka
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Division of Genetic Counseling, Kobe University Hospital, Kobe, Japan.|Department of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.|Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D001483:Base Sequence / Q000235:genetics*; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics; D004827:Epilepsy / Q000235:genetics; D059472:Exome / Q000235:genetics; D019066:Facies; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D012640:Seizures; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D017261:Glycosylphosphatidylinositols; C561296:PIGN protein, human; D010770:Phosphotransferases
keywords: PIGN; developmental defect; genetic counseling; inherited GPI deficiency; prenatal diagnosis