title: PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels.
abstract: Aberrations in the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway constitute a subclass of congenital disorders of glycosylation, and mutations in seven genes involved in this pathway have been identified. Among them, mutations in PIGV and PIGO, which are involved in the late stages of GPI-anchor synthesis, and PGAP2, which is involved in fatty-acid GPI-anchor remodeling, are all causative for hyperphosphatasia with mental retardation syndrome (HPMRS). Using whole exome sequencing, we identified novel compound heterozygous PIGO mutations (c.389C>A [p.Thr130Asn] and c.1288C>T [p.Gln430*]) in two siblings, one of them having epileptic encephalopathy. GPI-anchored proteins (CD16 and CD24) on blood granulocytes were slightly decreased compared with a control and his mother. Our patients lacked the characteristic features of HPMRS, such as facial dysmorphology (showing only a tented mouth) and hypoplasia of distal phalanges, and had only a mild elevation of serum alkaline phosphatase (ALP). Our findings therefore expand the clinical spectrum of GPI-anchor deficiencies involving PIGO mutations to include epileptic encephalopathy with mild elevation of ALP.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Rie
authors.initials: R
authors.lastname: Anzai
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kodera
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000097:blood*; D002648:Child; D002658:Developmental Disabilities / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D004827:Epilepsy / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000097:blood / Q000172:deficiency; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000175:diagnosis; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010760:Phosphorus Metabolism Disorders / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D012640:Seizures; D012720:Severity of Illness Index
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C485854:PIGO protein, human; D000469:Alkaline Phosphatase
keywords: Congenital disorders of glycosylation; Epileptic encephalopathy; Glycosylphosphatidylinositol anchors; PIGO