Pyle disease - Functional validation of disease-causing missense variants in SFRP4/sFRP4.
Lex Magnus, Ewa Hordyjewska-Kowalczyk, Anna Sowińska-Seidler et al.
✦ AI-curated · Sources linked
Case in brief
An adult woman presented with clinical and radiographic features of Pyle disease, including Erlenmeyer-flask deformity, cortical thinning, and multiple fractures. Genetic testing revealed a novel homozygous missense variant in SFRP4, which is located in the WNT-binding domain. Functional studies demonstrated that this variant impairs the inhibitory function of sFRP4 on WNT signaling, similar to previously reported variants.
Diagnostic / clinical pearl
Missense variants in SFRP4 can impair its function similarly to truncating variants, expanding the mutational spectrum of Pyle disease.
Why it matters
Understanding the functional impact of missense variants in SFRP4 may enhance diagnostic accuracy for families affected by Pyle disease.