Expanding the clinical spectrum of PPP3CA variants
Author Information
Author(s): Castiglioni Silvia, Pezzoli Laura, Pezzani Lidia, Lettieri Antonella, Di Fede Elisabetta, Cereda Anna, Ancona Silvia, Gallina Andrea, Colombo Elisa Adele, Parodi Chiara, Grazioli Paolo, Taci Esi, Milani Donatella, Iascone Maria, Massa Valentina
Primary Institution: Università degli Studi di Milano
Hypothesis
The study investigates the effects of two de novo variants in the PPP3CA gene on clinical manifestations and cellular behavior.
Conclusion
The study suggests that aberrant PPP3CA protein in one patient leads to increased cell death, while the other patient exhibits a milder phenotype due to an imbalance between isoforms.
Supporting Evidence
- Two de novo variants in PPP3CA were identified through whole exome sequencing.
- Patient-derived cell lines showed altered expression of PPP3CA isoforms.
- Patient 1 exhibited reduced proliferation and increased cell death.
- Patient 2 showed moderate developmental delay and improved speech over time.
- UPR pathway activation was observed in both patients' lymphoblastoid cell lines.
Takeaway
Researchers found two patients with different problems caused by changes in a gene called PPP3CA, which affects how their cells work.
Methodology
Whole exome sequencing was performed on DNA from patients and their parents, followed by Sanger sequencing for variant confirmation.
Limitations
The study is limited by the small sample size and the need for further research to clarify the mechanisms behind the observed phenotypes.
Participant Demographics
Two male patients of Caucasian ethnicity from non-consanguineous Italian couples.
Statistical Information
P-Value
p=0.01 for isoform 1 expression in Pt.1; p=9.2E-05 for isoform 2 expression in Pt.1; p=0.02 for isoform 2 expression in Pt.2.
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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