Bidirectional Sanger sequencing was performed for targeted mutation detection in the KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, and PRKACA genes using DNA extracted from the tumor tissues of the 22 A/CPA patients.
Further, no ATP1A1, ATP2B3, CACNA1D, or CACNA1H mutations were detected.
Osswald et al., "Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension," Nature Genetics, vol.
This work then led to the discovery of various plasma membrane channel mutations [sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1), plasma membrane calcium-transporting ATPase 3 (ATP2B3), and voltage-dependent calcium channel type L alpha 1D subunit (CACNA1D)] in other APAs.
Michael Stowasser: The identification of these KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations has greatly enhanced knowledge regarding the roles of these channels in adrenal physiology and pathophysiology and has the potential to lead to new diagnostic and therapeutic strategies.
 Human genes: KCNJ5, potassium inwardly-rectifying channel subfamily J member 5; ATP1A1, sodium/potassium-transporting ATPase subunit alpha-1; ATP2B3, plasma membrane calcium-transporting ATPase 3; CACNA1D, voltage-dependent calcium channel type L alpha 1D subunit.
During the past 2 years, considerable interest has been generated by the discovery of sporadic mutations in potassium channels (KCNJ5), calcium channels (CACNA1D), and ATPases (ATP1A1 and ATP2B3; Figure 2, C).
ATP1A1 (encoding [Na.sup.+]/[K.sup.+] ATPase a subunit) and ATP2B3 (encoding [Ca.sup.2+]ATPase) play an important role in the regulation of aldosterone production by maintaining cell membrane potential.