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Hypertension linked to PDE3A activation

Nature Genetics volume 47, pages 562–563 (2015)Cite this article

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A new study identifies PDE3A mutations as the cause of brachydactyly type E with hypertension. These mutations alter PDE3A activity by uncovering cryptic sites for phosphorylation by PKA and PKC, leading to enzyme hyperactivation that abnormally lowers cAMP levels.

Brachydactyly (shortness of fingers and toes) is a defining feature of a cluster of rare conditions inherited in an autosomal dominant pattern. In most cases, this phenotype does not cause health problems. However, when brachydactyly occurs with other anomalies, serious health issues can arise, such as in autosomal dominant brachydactyly type E with hypertension (HTNB; MIM 112410). In this syndrome, affected individuals exhibit shortened digits and develop severely high blood pressure in childhood, which, if untreated, causes stroke before 50 years of age.

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Figure 1: HTNB-associated mutations alter PDE3A activity.

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  1. Miles Houslay is at the Institute of Pharmaceutical Science, King's College London, London, UK, and Mironid, Ltd., BioCity Scotland, Newhouse, UK.,

    Miles Houslay

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Correspondence to Miles Houslay.

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Houslay, M. Hypertension linked to PDE3A activation. Nat Genet 47, 562–563 (2015). https://doi.org/10.1038/ng.3316

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