Congenital Disorders of Glycosylation

Gene: PIGL

Green List (high evidence)

Glycosylphosphatidylinositol (GPI) is used as a membrane anchor by many eukaryotic cell surface proteins. The first step in GPI biosynthesis involves the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). The second step is N-deacetylation of GlcNAc-PI, which is performed by PIGL.

Bi-allelic variants in PIGL have been associated with a multisystem disorder clinically characterised by colobomas, congenital heart defects, migratory ichthyosiform dermatosis, mental retardation, and ear anomalies (CHIME). Other clinical features include distinctive facial features, abnormal growth, genitourinary abnormalities, seizures, and feeding difficulties. Some individuals have hyperphosphatasia.

p.Leu167Pro is a common founder variant. Also note large deletion reported more than once.

More than 10 unrelated families reported.

Created: 19 Dec 2020, 6:32 a.m. | Last Modified: 19 Dec 2020, 6:32 a.m.

Panel Version: 0.270

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CHIME syndrome, MIM# 280000, MONDO:0010221

Publications

• 22444671
• 31535386
• 30023290
• 29473937
• 28371479
• 25706356