Somatic Mosaicism Modulating Clinical Severity in COL2A1-Related Skeletal Dysplasia: A Case of Profound Skeletal Asymmetry.

Abstract

Type II collagenopathies represent a broad spectrum of skeletal dysplasias caused by pathogenic variants in the COL2A1 gene, ranging from perinatally lethal achondrogenesis type II to milder phenotypes such as spondyloepiphyseal dysplasia congenita and Stickler syndrome. Although specific mutations may suggest certain phenotypic trends, the genotype-phenotype relationship is not fully clarified. We describe a patient with marked skeletal asymmetry due to somatic mosaicism for a pathogenic COL2A1 variant (c.G1537A; p.G513S) previously associated with lethal phenotypes. The mutation, identified in mosaic form with an alternative allele ratio of 36:17, likely accounts for the asymmetric and nonlethal presentation. We also included a review of previously reported mosaic cases in the literature, highlighting the underrecognized role of mosaicism in modulating disease severity and laterality in COL2A1-related skeletal dysplasias.