A novel PGAP1 splice-site variant expanding the clinical and molecular spectrum of GPI-anchor disorders.
Seyyed-Saleh Hashemi, Reza Moazzami, Ali Miri
✦ AI-curated · Sources linked
Case in brief
A patient with neurodevelopmental impairment was found to carry a novel homozygous PGAP1 splice-site variant, NM_024989.4.1173 + 1G > A. The variant was absent from public databases and classified as likely pathogenic under ACMG guidelines. In silico splice-prediction tools consistently indicated substantial disruption, and structural modeling suggested conformational changes associated with a predicted in-frame deletion. Segregation analysis supported the inheritance assessment. The report links the variant to PGAP1-related GPI-anchor disorder and adds to the described clinical and molecular spectrum.
What made this case unusual
The reported homozygous splice-site variant was predicted to disrupt splicing while producing a predicted in-frame deletion with associated structural changes.
Diagnostic / clinical pearl
Consider genomic analysis in unexplained neurodevelopmental impairment; a PGAP1 variant may provide a molecular diagnosis, with segregation and computational analyses contributing to variant assessment.