Journal
NEUROGENETICS
Volume 15, Issue 3, Pages 193-200Publisher
SPRINGER
DOI: 10.1007/s10048-014-0408-y
Keywords
Whole exome sequencing; PIGT; Compound heterozygous mutations; Glycosylphosphatidylinositol-anchored protein; Multiple congenital anomalies-hypotonia-seizures syndrome 3; Hypophosphatasia
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Funding
- Ministry of Health, Labour and Welfare of Japan
- Japan Society for the Promotion of Science
- Takeda Science Foundation
- fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems
- Strategic Research Program for Brain Sciences
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [25860874, 24118001] Funding Source: KAKEN
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Recessive mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor synthesis pathway have been demonstrated as causative of GPI deficiency disorders associated with intellectual disability, seizures, and diverse congenital anomalies. We performed whole exome sequencing in a patient with progressive encephalopathies and multiple dysmorphism with hypophosphatasia and identified novel compound heterozygous mutations, c.250G > T (p. Glu84*) and c.1342C > T (p. Arg488Trp), in PIGT encoding a subunit of the GPI transamidase complex. The surface expression of GPI-anchored proteins (GPI-APs) on patient granulocytes was lower than that of healthy controls. Transfection of the Arg488Trp mutant PIGT construct, but not the Glu84* mutant, into PIGT-deficient cells partially restored the expression of GPI-APs DAF and CD59. These results indicate that PIGT mutations caused neurological impairment and multiple congenital anomalies in this patient.
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