2. Academic Validation
  3. Congenital disorder of glycosylphosphatidylinositol (GPI)-anchor biosynthesis--The phenotype of two patients with novel mutations in the PIGN and PGAP2 genes

Congenital disorder of glycosylphosphatidylinositol (GPI)-anchor biosynthesis--The phenotype of two patients with novel mutations in the PIGN and PGAP2 genes

  • Eur J Paediatr Neurol. 2016 May;20(3):462-73. doi: 10.1016/j.ejpn.2016.01.007.
Aleksandra Jezela-Stanek 1,  Elżbieta Ciara 2,  Dorota Piekutowska-Abramczuk 2,  Joanna Trubicka 2,  Elżbieta Jurkiewicz 3,  Dariusz Rokicki 4,  Hanna Mierzewska 5,  Justyna Spychalska 6,  Małgorzata Uhrynowska 6,  Marta Szwarc-Bronikowska 4,  Piotr Buda 4,  Abdul Rahim Said 7,  Ewa Jamroz 8,  Małgorzata Rydzanicz 9,  Rafał Płoski 9,  Małgorzata Krajewska-Walasek 2,  Ewa Pronicka 10
Affiliations

Affiliations

  • 1 Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland. Electronic address: jezela@gmail.com.
  • 2 Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
  • 3 Department of Diagnostic Imaging, The Children's Memorial Health Institute, Warsaw, Poland.
  • 4 Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
  • 5 Department of Child and Adolescent Neurology, Institute of Mother and Child, Warsaw, Poland.
  • 6 Department of Immunology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
  • 7 Children's Home Hospice, Opole, Poland.
  • 8 Department of Pediatrics and Developmental Age Neurology, Medical University of Silesia, Katowice, Poland.
  • 9 Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
  • 10 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.
PMID: 26879448 DOI: 10.1016/j.ejpn.2016.01.007
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.

Patients and 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.

Keywords

Congenital disorders of glycosylation; Flow cytometry; GPI-anchor deficiency; PGAP2 gene; PIGN gene.

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