| Title: |
In-Depth Phenotyping of PIGW-Related Disease and Its Role in 17q12 Genomic Disorder |
| Authors: |
Agnese Feresin, Mathilde Lefebvre, Emilie Sjøstrøm, Caterina Zanus, Elisa Paccagnella, Irene Bruno, Erica Valencic, Anna Morgan, Alberto Tommasini, Christel Thauvin, Allan Bayat, Giorgia Girotto, Luciana Musante |
| Source: |
Biomolecules, Vol 14, Iss 12, p 1626 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Microbiology |
| Subject Terms: |
PIGW, GPIBD11, heart malformation, epilepsy, fetus, 17q12 genomic disorder, Microbiology, QR1-502 |
| More Details: |
Glycosylphosphatidylinositol (GPI) biosynthesis defect 11 (GPIBD11), part of the heterogeneous group of congenital disorders of glycosylation, is caused by biallelic pathogenic variants in PIGW. This rare disorder has previously been described in only 12 patients. We report four novel patients: two sib fetuses with congenital anomalies affecting several organs, including the heart; a living girl with tetralogy of Fallot, global developmental delay, behavioral abnormalities, and atypic electroencephalography (EEG) without epilepsy; a girl with early-onset, treatment-resistant seizures, developmental regression, and recurrent infections, that ultimately passed away prematurely due to pneumonia. We also illustrate evolving facial appearance and biochemical abnormalities. We identify two novel genotypes and the first frameshift variant, supporting a loss-of-function pathogenic mechanism. By merging our cohort with patients documented in the literature, we deeply analyzed the clinical and genetic features of 16 patients with PIGW-related disorder, revealing a severe multisystemic condition deserving complex management and with uncertain long-term prognosis. We consider the role of PIGW within the critical 17q12 region, which is already associated with genomic disorders caused by deletion or duplication and characterized by variable expressivity. Finally, we discuss PIGW dosage effects and a second hit hypothesis in human development and disease. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2218-273X |
| Relation: |
https://www.mdpi.com/2218-273X/14/12/1626; https://doaj.org/toc/2218-273X |
| DOI: |
10.3390/biom14121626 |
| Access URL: |
https://doaj.org/article/1c2eb7676e8c4279acfc964b2270ec3c |
| Accession Number: |
edsdoj.1c2eb7676e8c4279acfc964b2270ec3c |
| Database: |
Directory of Open Access Journals |
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