title: A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family.
abstract: PGAP2 (Post-GPI Attachment to Proteins 2) gene is involved in lipid remodeling steps of Glycosylphosphatidylinositol (GPI)-anchor maturation. At the surface of the cell this gene is required for proper expression of GPI-anchored proteins. Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation. Mutations in the PGAP2 gene cause hyperphosphatasia mental retardation syndrome-3. We have identified a large consanguineous family from Saudi origin segregating developmental delay, intellectual disability, epilepsy and microcephaly. Whole exome sequencing with 100× coverage was performed on two affected siblings of the family. Data analysis in the patient revealed a novel missense mutation c.191C>T in PGAP2 gene resulting in Alanine to Valine substitution (Ala64Val). The mutation was reconfirmed and validated by subsequent Sanger sequencing method. The mutation was ruled out in 100 unrelated healthy controls. We suggest that this pathogenic mutation disrupts the proper function of the gene proteins resulting in the disease state.
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589 Jeddah, Saudi Arabia. Electronic address: mimrannaseer@yahoo.com.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Naseer
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.affiliation: Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Box 80215, Jeddah 21589, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Jan
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
authors.forename: Adeel G
authors.initials: AG
authors.lastname: Chaudhary
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
authors.forename: Peter Natesan
authors.initials: PN
authors.lastname: Pushparaj
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589 Jeddah, Saudi Arabia; KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Abuzenadah
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Al-Qahtani
mesh_terms: D001921:Brain / Q000503:physiopathology; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005190:Family; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012529:Saudi Arabia
chemical_list: D009687:Nuclear Proteins; C484441:PGAP2 protein, human
keywords: Developmental delay; Epilepsy; Intellectual disability; Microcephaly; PGAP2