title: A PIGN mutation responsible for multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) in an Israeli-Arab family.
abstract: Mutations in the PIGN gene involved in the glycosylphoshatidylinositol (GPI) anchor biosynthesis pathway cause Multiple Congenital Anomalies-Hypotonia-Seizures syndrome 1 (MCAHS1). The syndrome manifests developmental delay, hypotonia, and epilepsy, combined with multiple congenital anomalies. We report on the identification of a homozygous novel c.755A>T (p.D252V) deleterious mutation in a patient with Israeli-Arab origin with MCAHS1. The mutated PIGN caused a significant decrease of the overall GPI-anchored proteins and CD24 expression. Our results, strongly support previously published data, that partial depletion of GPI-anchored proteins is sufficient to cause severe phenotypic expression.
authors.affiliation: Genetics Institute, Ha'Emek Medical center, Afula, Israel.
authors.forename: Morad
authors.initials: M
authors.lastname: Khayat
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joseph Mark
authors.initials: JM
authors.lastname: Tilghman
authors.affiliation: Genetics Institute, Ha'Emek Medical center, Afula, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Chervinsky
authors.affiliation: The Hematology Laboratory, Ha'Emek Medical center, Afula, Israel.
authors.forename: Lucia
authors.initials: L
authors.lastname: Zalman
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Genetics Institute, Ha'Emek Medical center, Afula, Israel.|Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D001483:Base Sequence; D051927:CD24 Antigen / Q000096:biosynthesis; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007557:Israel; D009123:Muscle Hypotonia / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010770:Phosphotransferases / Q000235:genetics*; D012640:Seizures / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; D017261:Glycosylphosphatidylinositols; C561296:PIGN protein, human; D010770:Phosphotransferases
keywords: Exome sequencing; MCAHS1; PIGN; glycosylphoshatidylinositol (GPI)