MMP13 – Metaphyseal Anadysplasia

Metaphyseal Anadysplasia is a rare chondrodysplasia characterized by early-onset metaphyseal dysplasia and short stature that partially improves with age. The MMP13 gene encodes matrix metalloproteinase 13, critical for collagen type II turnover in growth plate cartilage. In a consanguineous family, two affected siblings presented with persistent short stature and mixed metaphyseal and epiphyseal dysplasia; whole-exome sequencing identified a homozygous nonsense variant, c.325C>T (p.Arg109Ter), abolishing MMP13 function (PMID:24781753). This finding extends the mutational spectrum to include autosomal recessive nonsense mutations and supports a loss-of-function mechanism.

Evidence is limited to a single family with two AR probands, no additional informative segregation, and absence of in vivo or in vitro functional validation beyond truncation predictions. Additional unrelated cases and experimental studies are required to confirm the association and elucidate pathogenic mechanisms.

References

• European journal of human genetics • 2015 • Exome sequencing reveals a nonsense mutation in MMP13 as a new cause of autosomal recessive metaphyseal anadysplasia. PMID:24781753

Evidence Based Scoring (AI generated)