COL11A1 – Fibrochondrogenesis 1

Fibrochondrogenesis 1 is an autosomal recessive lethal skeletal dysplasia characterized by short-limbed growth and flattened vertebral bodies. Mutations in the gene encoding the α1 chain of type XI collagen, COL11A1, are the primary molecular cause. In a consanguineous Iranian family, one proband—an 18-week male aborted fetus—harbored a novel homozygous missense variant c.3440G>A (p.Gly1147Asp) in COL11A1 identified by whole-exome sequencing (one proband PMID:36397853). Sanger sequencing confirmed the variant and in silico tools predicted disruption of the conserved Gly-Xaa-Yaa helical motif. No additional unrelated cases or segregation data have been reported to date. Functional validation for this specific variant is lacking, although glycine substitutions in collagen triple helices are a recognized pathogenic mechanism. Further familial studies and cellular or animal models are required to substantiate the genotype–phenotype correlation and support diagnostic implementation. Key Take-home: Preliminary case-level evidence implicates a COL11A1 glycine substitution in fibrochondrogenesis 1, pending confirmatory genetic and functional data.

References

• Clinical case reports • 2022 • Clinical whole-exome sequencing analysis reveals a novel missense COL11A1 mutation resulting in an 18-week Iranian male aborted fetus with Fibrochondrogenesis 1: A case report PMID:36397853

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