Variable skeletal phenotypes associated with biallelic variants in PRKG2

Although disruption of PRKG2 has been shown to cause skeletal anomalies and/or dwarfism in rodents, cattle and dogs, only two human patients have been reported in the medical literature so far.  In this study, four individuals with rare PRKG2 variants are described.  In one family, the variant lies close to the end of the gene; in these subjects, detailed clinical/radiological assessment help extend the phenotypic range associated with this condition to involve the spine (flattened vertebrae) but without significant shortening of the distal limb segments.  Functional testing indicates that the variants affect the biological MAPK signalling pathway to a similar extent.  Interestingly, one of the individuals had a more severe “blended” phenotype due to an additional COL1A1 mutation leading to multiple fractures. (By Dr. Alistair Pagnamenta, )

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