0013676 2025 RIV DK eng J
Schnur, R.E. - Dvořáček, Lukáš - Kalsner, L. - Shapiro, F.L. - Grebeňová, Dana - Yanni, D. - Wasserman, B.N. - VIGOR: Virtual Genome Center for Infant Health - Dyer, L.M. - Antonarakis, S.E. - Kuželová, Kateřina^G
New kinase-deficient PAK2 variants associated with Knobloch syndrome type 2.
Clinical genetics. Vol. 106, no. 4 (2024), s. 518-524. ISSN 0009-9163
Institucionální podpora: RVO:00023736
Klíčová slova: PAK2 * meningocele * retinal detachment
Cite Score: 5.400, rok: 2024; SJR: 1.093, rok: 2024; IF: 2.3, rok: 2024
DOI: 10.1111/cge.14578

Anotace: The p21-activated kinase (PAK) family of proteins regulates various processes requiring dynamic cytoskeleton organization such as cell adhesion, migration, proliferation, and apoptosis. Among the six members of the protein family, PAK2 is specifically involved in apoptosis, angiogenesis, or the development of endothelial cells. We report a novel de novo heterozygous missense PAK2 variant, p.(Thr406Met), found in a newborn with clinical manifestations of Knobloch syndrome. In vitro experiments indicated that this and another reported variant, p.(Asp425Asn), result in substantially impaired protein kinase activity. Similar findings were described previously for the PAK2 p.(Glu435Lys) variant found in two siblings with proposed Knobloch syndrome type 2 (KNO2). These new variants support the association of PAK2 kinase deficiency with a second, autosomal dominant form of Knobloch syndrome: KNO2.