Dataset Information

Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

ABSTRACT: Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subclass of congenital disorders of glycosylation. Here we performed whole-exome sequencing in an individual with cerebral visual impairment (CVI), intellectual disability (ID), and factor XII deficiency and revealed compound heterozygous variants in PGAP1, c.274_276del (p.(Pro92del)) and c.921_925del (p.(Lys308Asnfs*25)). Subsequently, PGAP1-deficient Chinese hamster ovary (CHO)-cell lines were transfected with either mutant or wild-type constructs and their sensitivity to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment was measured. The mutant constructs could not rescue the PGAP1-deficient CHO cell lines resistance to PI-PLC treatment. In addition, lymphoblastoid cell lines (LCLs) of the affected individual showed no sensitivity to PI-PLC treatment, whereas the LCLs of the heterozygous carrier parents were partially resistant. In conclusion, we report novel PGAP1 variants in a boy with CVI and ID and a proven functional loss of PGAP1 and show, to our knowledge, for the first time this genetic association with CVI.

SUBMITTER: Bosch DG

PROVIDER: S-EPMC4795198 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

Bosch Daniëlle G M DG Boonstra F Nienke FN Kinoshita Taroh T Jhangiani Shalini S de Ligt Joep J Cremers Frans P M FP Lupski James R JR Murakami Yoshiko Y de Vries Bert B A BB

European journal of human genetics : EJHG 20150325 12

Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subclass of congenital disorders of glycosylation. Here we performed whole-exome sequencing in an individual with cerebral visual impairment (CVI), intellectual disability (ID), and factor XII deficiency ...[more]

PMID: 25804403

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Dataset Information

Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

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Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

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