Document Type
Article
Publication Date
1-28-2025
Publication Title
American journal of medical genetics. Part A
Keywords
JGM
JAX Source
Am J Med Genet A. Forthcoming 2025:e64006.
First Page
64006
Last Page
64006
ISSN
1552-4833
PMID
39876536
DOI
https://doi.org/10.1002/ajmg.a.64006
Grant
P.A.A. was sup- ported by NIH NIGMS R35GM133600 and NIH NCI P30CA034196
Abstract
P21-activated kinase 2 (PAK2) is a serine/threonine kinase essential for a variety of cellular processes including signal transduction, cellular survival, proliferation, and migration. A recent report proposed monoallelic PAK2 variants cause Knobloch syndrome type 2 (KNO2)-a developmental disorder primarily characterized by ocular anomalies. Here, we identified a novel de novo heterozygous missense variant in PAK2, NM_002577.4:c.1273G>A, p.(D425N), by genome sequencing in an individual with features consistent with KNO2. Notable clinical phenotypes observed in this individual were global developmental delay, congenital retinal detachment, mild cerebral ventriculomegaly, hypotonia, failure to thrive, pyloric stenosis, feeding intolerance, patent ductus arteriosus, and mild facial dysmorphism. The p.(D425N) variant lies within the protein kinase domain and is predicted to be functionally damaging by in silico analysis. Previous clinical genetic testing did not report this variant due to unknown relevance of PAK2 variants at the time of testing, highlighting the importance of reanalysis. Our findings substantiate the candidacy of PAK2 variants in KNO2 and expand the KNO2 clinical phenotypic spectrum.
Recommended Citation
Werren E,
Kalsner L,
Ewald J,
Peracchio M,
King C,
Vats P,
Audano P,
Robinson P,
Adams M,
Kelly M,
Matson A.
Phenotypic Expansion of Knobloch Syndrome Type 2 in an Individual With a De Novo PAK2 Variant. Am J Med Genet A. Forthcoming 2025:e64006.