8q22.2 Deletion

Deng et al. “Heterozygous loss of OSR2 can cause radioulnar synostosis with ancillary skeletal manifestations”. “Genetics in Medicine” 2026, v. 28(3), 101664.

Congenital radioulnar synostosis (RUS) is defined by bony fusion of the proximal radius and ulna bones. Genetic causes have previously been identified such as pathogenic variants in SMAD6 and MECOM. However, approximately 60% of RUS cases lack a molecular diagnosis. Deng et al. highlight how 8q22.2q22.3 microdeletion syndrome can present with skeletal anomalies such as RUS. The authors present a case of an 8q22.2 microdeletion encompassing the gene OSR2, along with five familial cases of OSR2 variants, to suggest that OSR2 haploinsufficiency or loss-of-function variants can result in RUS and/or other skeletal malformations. A mother-son duo were identified to have a 383.28-kb heterozygous deletion at 8q22.2 on chromosomal microarray; both individuals had RUS. Including the familial cases of identified OSR2 variants identified on exome sequencing, the authors appreciated other skeletal anomaly phenotypes: hypoplasia of the distal ulna and excessive inclination of the distal radius (1/13), polyarticular stiffness (3/13), short stature (4/13), ear deformity (3/13), and mild scoliosis (1/13), spina bifida occulta (1/13), trapeziometacarpal dislocation (1/13), and tall stature (1/13). These findings suggest that OSR2 variants may be associated not only with RUS but also with a broader spectrum of skeletal anomalies. The authors further describe existing mouse model studies that support the role of OSR2 in human joint fusion. However, larger cohort studies are needed to confirm the roles OSR2 plays in the greater observed skeletal malformations.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. Review and formatting by Nicole Talaba, MS CGC. For more information on any article please contact info@chromodisorder.org