title: Congenital disorder of glycosylphosphatidylinositol (GPI)-anchor biosynthesis--The phenotype of two patients with novel mutations in the PIGN and PGAP2 genes.
abstract: BACKGROUND
  Glycosylphosphatidylinositol (GPI)-anchor deficiencies are a new subclass of congenital disorders of glycosylation. About 26 genes are involved in the GPI-anchor biosynthesis and remodeling pathway, of which mutations in thirteen have been reported to date as causative of a diverse spectrum of intellectual disabilities. Since the clinical phenotype of these disorders varies and the number of described individuals is limited, we present new patients with inherited GPI-anchor deficiency (IGD) caused by mutations in the PGAP2 and PIGN genes.
  
  
  METHODS
  The first girl presented with profound psychomotor retardation, low birth parameters, and chest deformities already existing in neonatal period. The disease course was slowly progressive with severe hypotonia, chronic fever, and respiration insufficiency at the age of 6. The second girl showed profound psychomotor retardation, marked hypotonia, and high birth weight (97 centile). Dysmorphy was mild or absent in both girls. Whole exome sequencing revealed novel variants in the genes PGAP2 (c.2T>G and c.221G>A) and PIGN (c.790G>A and c.932T>G). Impaired GPI binding were was subsequently uncovered, although the hyperactivity of alkaline phosphatase (a GPI-anchored protein) occurred only in first case.
  
  
  CONCLUSIONS
  Based on our results we can conclude that: 1. GPI-anchor biosynthesis disorders may represent a relatively frequent and overlooked metabolic defect; 2. The utility of GPI binding assessment as a screening test for this group of rare diseases requires further studies.
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland. Electronic address: jezela@gmail.com.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jezela-Stanek
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Ciara
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trubicka
authors.affiliation: Department of Diagnostic Imaging, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Jurkiewicz
authors.affiliation: Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rokicki
authors.affiliation: Department of Child and Adolescent Neurology, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Mierzewska
authors.affiliation: Department of Immunology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Spychalska
authors.affiliation: Department of Immunology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Uhrynowska
authors.affiliation: Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Szwarc-Bronikowska
authors.affiliation: Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Buda
authors.affiliation: Children's Home Hospice, Opole, Poland.
authors.forename: Abdul Rahim
authors.initials: AR
authors.lastname: Said
authors.affiliation: Department of Pediatrics and Developmental Age Neurology, Medical University of Silesia, Katowice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jamroz
authors.affiliation: Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.affiliation: Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland; Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pronicka
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002675:Child, Preschool; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics*; D017261:Glycosylphosphatidylinositols / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009123:Muscle Hypotonia / Q000209:etiology; D009154:Mutation; D010641:Phenotype; D010770:Phosphotransferases / Q000235:genetics*; D012640:Seizures
chemical_list: D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; C561296:PIGN protein, human; D010770:Phosphotransferases; D000469:Alkaline Phosphatase
keywords: Congenital disorders of glycosylation; Flow cytometry; GPI-anchor deficiency; PGAP2 gene; PIGN gene