Congenital disorder of glycosylphosphatidylinositol (GPI)-anchor biosynthesis - the phenotype of two patients with novel mutations in the PIGN and PGAP2 genes.
PBN-AR
Instytucja
Instytut "Pomnik - Centrum Zdrowia Dziecka"
Informacje podstawowe
Główny język publikacji
en
Czasopismo
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
ISSN
1090-3798
EISSN
1532-2130
Wydawca
London ; Philadelphia : Saunders
Rok publikacji
2016
Numer zeszytu
3
Strony od-do
462-473
Numer tomu
20
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
en
congenital disorders of glycosylation
flow cytometry
GPI-anchor deficiency
PGAP2 gene
PIGN gene
Streszczenia
Język
en
Treść
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.
Cechy publikacji
case-study
Inne
System-identifier
0000014979
CrossrefMetadata from Crossref logo
Cytowania
Liczba prac cytujących tę pracę
Brak danych
Referencje
Liczba prac cytowanych przez tę pracę
Brak danych