title: Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3.
abstract: Recessive mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor synthesis pathway have been demonstrated as causative of GPI deficiency disorders associated with intellectual disability, seizures, and diverse congenital anomalies. We performed whole exome sequencing in a patient with progressive encephalopathies and multiple dysmorphism with hypophosphatasia and identified novel compound heterozygous mutations, c.250G>T (p. Glu84*) and c.1342C>T (p. Arg488Trp), in PIGT encoding a subunit of the GPI transamidase complex. The surface expression of GPI-anchored proteins (GPI-APs) on patient granulocytes was lower than that of healthy controls. Transfection of the Arg488Trp mutant PIGT construct, but not the Glu84* mutant, into PIGT-deficient cells partially restored the expression of GPI-APs DAF and CD59. These results indicate that PIGT mutations caused neurological impairment and multiple congenital anomalies in this patient.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kashii
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D009123:Muscle Hypotonia / Q000150:complications / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012640:Seizures / Q000150:complications / Q000235:genetics*; D013577:Syndrome
chemical_list: D017261:Glycosylphosphatidylinositols; D000217:Acyltransferases; C081007:COOH-terminal signal transamidase