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Autosomal dominant Stickler syndrome is typically caused by collagen gene mutations, but a novel role for BMP4 has been identified. In one family, a heterozygous BMP4 nonsense variant, c.130G>T (p.Gly44Ter), segregated with retinal detachment and renal dysplasia in four affected relatives ([PMID:30568244]). No pathogenic variants were detected in COL2A1 or COL11A1. Skin fibroblast mRNA analysis revealed that the mutant transcript escapes nonsense-mediated decay, supporting production of a truncated BMP4 protein. BMP4 is a critical growth factor for eye development in animal models, concordant with the human phenotype. Given segregation in a single kindred and limited functional follow-up, we classify the BMP4–Stickler syndrome association as Limited evidence. Key Take-home: BMP4 should be considered in diagnostic gene panels for autosomal dominant Stickler syndrome.
Gene–Disease AssociationLimitedSingle family with a heterozygous BMP4 loss-of-function variant segregating with Stickler syndrome and renal dysplasia ([PMID:30568244]) Genetic EvidenceLimitedNovel heterozygous nonsense variant (c.130G>T (p.Gly44Ter)) segregating in one autosomal dominant family (4 affected) ([PMID:30568244]) Functional EvidenceLimitedSkin fibroblast mRNA studies showed absence of nonsense-mediated decay; animal models support BMP4 role in eye development |