Case report of a child bearing a novel deleterious splicing variant in PIGT
Por:
Mason S, Castilla-Vallmanya L, James C, Andrews PI, Balcells S, Grinberg-Vaisman DR, Kirk EP and Urreizti R
Publicada:
1 feb 2019
Categoría:
Medicine (miscellaneous)
Resumen:
Rationale: Trio family-based whole exome sequencing (WES) is a powerful tool in the diagnosis of rare neurodevelopmental diseases, even in patients with the unclear diagnosis. There have been previous reports of variants in the phosphatidylinositol glycan anchor biosynthesis class T (PIGT) gene associated with multiple congenital anomalies, with a total of 14 affected individuals across 8 families.
Patient concerns: An 18-month-old boy of Greek ancestry presented with global developmental delay, generalized tonic-clonic seizures, hypotonia, renal cysts, esotropia, bilateral undescended testes, bilateral vesicoureteric reflux, marked cardiac dextroposition, bilateral talipes equinovarus, and dysmorphic features.
Diagnosis: WES revealed 2 compound heterozygous variants in the PIGT gene, c.[494-2A>G]; [547A>C]/p.[Asp122Glyfs*35]; [Thr183Pro]. The splicing mutation was demonstrated to lead to the skipping of exon 4.
Interventions: Seizures, infections, and other main symptoms were treated.
Outcomes: The patient died at 2 years of age before the molecular diagnosis was achieved. Genetic counseling has been offered to the family.
Lessons: Most of the clinical features of the patient are in agreement with the previously described PIGT cases corroborating the usefulness of WES as a diagnostic tool.
Filiaciones:
Mason S:
Centre for Clinical Genetics, Sydney Children's Hospital Randwick, Sydney, Australia
Castilla-Vallmanya L:
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, IBUB, Institut de Recerca Sant Joan de Déu (IRSJD), CIBERER, Barcelona, Spain
James C:
Department of General Paediatrics
Andrews PI:
Department of Neurology, Sydney Children's Hospital
Balcells S:
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, IBUB, Institut de Recerca Sant Joan de Déu (IRSJD), CIBERER, Barcelona, Spain
Grinberg-Vaisman DR:
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, IBUB, Institut de Recerca Sant Joan de Déu (IRSJD), CIBERER, Barcelona, Spain
Kirk EP:
Centre for Clinical Genetics, Sydney Children's Hospital Randwick, Sydney, Australia
NSW Health Pathology East, Genetics Laboratory
School of Women's and Children's Health, University of New South Wales, Randwick, Sydney, Australia
Urreizti R:
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, IBUB, Institut de Recerca Sant Joan de Déu (IRSJD), CIBERER, Barcelona, Spain
Open Access
|