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In a single pedigree with Legg-Calve-Perthes disease (MONDO:0007885), a heterozygous COL2A1 mutation segregated with disease in four affected male relatives across two generations (PMID:24014797). However, targeted analysis of 119 radiologically confirmed Perthes disease patients revealed no COL2A1 mutations in any case (PMID:18978274). This conflicting evidence indicates that while COL2A1 variants may underlie LCPD in rare familial clusters, they are not a common cause of sporadic disease. No functional or animal model studies have yet linked COL2A1 dysfunction mechanistically to femoral head avascular necrosis in LCPD. Further large-scale genetic screens and functional assays are required to resolve this ambiguity. Key take-home: COL2A1 testing may be informative in multigenerational LCPD families but has limited diagnostic utility in unselected patients.
Gene–Disease AssociationDisputedSegregation in a single family with 4 affected ([PMID:24014797]) but no COL2A1 mutations in 119 LCPD patients ([PMID:18978274]) Genetic EvidenceLimitedOne pedigree with segregating variant in 4 cases; not replicated in larger cohort Functional EvidenceNoneNo functional studies linking COL2A1 variants to LCPD phenotype |