Preserved bone mineral density in autosomal dominant SP7-related osteogenesis imperfecta: a case report of the p.Glu340Ala variant.

= -1.05 kcal/mol), and conservation analysis across orthologs predicted a deleterious effect. The variant met six ACMG/AMP criteria (PS3, PM1, PM2, PP1, PP2, PP4) and was reclassified as pathogenic. Sanger sequencing confirmed variant presence in all affected individuals and absence in unaffected relatives, with Fisher's exact test demonstrating a significant association with the disease (p = 0.0083). This study represents the first family-based genetic investigation of OI in Malaysia and provides independent evidence that SP7-related OI can manifest as autosomal dominant disease with preserved bone mineral density and defective fracture healing. This supports a haploinsufficiency mechanism with important implications for genetic diagnosis and counseling.