COL11A2 – Fibrochondrogenesis

Two unrelated probands with fibrochondrogenesis were reported harboring distinct COL11A2 variants (PMID:22246659). The first case was a child of consanguineous parents with a homozygous splice donor mutation c.1719+1dup in intron 18 leading to exon 18 skipping and an in-frame 18–amino acid deletion in the triple-helical domain. The second case carried a de novo 9-bp deletion c.2902_2910del (p.Asp968_Gly970del) in exon 40. Both variants were absent from COL11A1 and localize to critical regions of the proα2(XI) chain of type XI collagen.

Functional assessment by exon-trapping confirmed that the intron 18 splice alteration causes exon 18 skipping, predicting loss of structural integrity in the collagen triple helix. The p.Asp968_Gly970del removes three conserved residues within the Gly-X-Y repeat, likely disrupting collagen fibrillogenesis. No conflicting reports have been published to date. Key take-home: Variants in COL11A2 can underlie both autosomal recessive and de novo dominant fibrochondrogenesis, supporting COL11A2 analysis in diagnostic workflows.

References

• American journal of medical genetics. Part A | 2012 | Dominant and recessive forms of fibrochondrogenesis resulting from mutations at a second locus, COL11A2. PMID:22246659

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