Congenital Disorders of Glycosylation

Gene: PIGW

Green List (high evidence)

OMIM - Glycosylphosphatidylinositol biosynthesis defect 11, AR

Function - Glycosylphosphatidylinositol (GPI) is a complex glycolipid that anchors many proteins to the cell surface. PIGW acts in the third step of GPI biosynthesis and acylates the inositol ring of phosphatidylinositol

Clingen - no association with CGD

PMID: 24367057 - (2013) - A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW.

PMID: 27626616 - (2016) Two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. The patients' phenotype is remarkably different from the phenotype of the only other described individual with PIGW mutations.

PMID: 30813920 - (2019) A Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations

PMID: 32198969 - (2020) A new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections.

Summary - Multiple unrelated families reported with different recessive variants either homozygous or compound heterozygous. Functional studies showed impaired enzymatic activity

Created: 15 Jul 2020, 12:30 a.m. | Last Modified: 15 Jul 2020, 12:33 a.m.

Panel Version: 0.57

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies

Publications

• PMID: 24367057
• 27626616
• 30813920
• 32198969