Paulien Terhal, Anton J Venhuizen, Davor Lessel, Wen-Hann Tan, Abdulrahman Alswaid, Regina Grün, Hamad I Alzaidan, Simon von Kroge, Nada Ragab, Maja Hempel, Christian Kubisch, Eduardo Novais, Alba Cristobal, Kornelia Tripolszki, Peter Bauer, Björn Fischer-Zirnsak, Rutger A J Nievelstein, Atty van Dijk, Peter Nikkels, Ralf Oheim, Heidi Hahn, Aida Bertoli-Avella, Madelon M Maurice, Uwe Kornak
Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in seven individuals from four families affected by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings included hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. In line with AXIN1 being a central component of the β-catenin destruction complex, analyses of primary and genome-edited cells harboring the truncating variants revealed enhanced basal canonical Wnt pathway activity...
September 7, 2023: American Journal of Human Genetics