Primary Aldosteronism via CACNA1H Gene

Primary aldosteronism is characterized by a constitutive overproduction of aldosterone (Dutta et al. 2016; Mulatero et al. 2013). It is the most common form of secondary hypertension and affects 8–13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH).

In addition to familial hyperaldosteronism types I, II and III, germline pathogenic variants in genes encoding voltage-gated calcium channels (CACNA1D and CACNA1H) can cause primary aldosteronism with or without neuromuscular abnormalities. In particular, compared with CACNA1D-causative primary aldosteronism, patients with CACNA1H defects present hypertension by age 10 years followed by no seizures or neurologic abnormalities (Scholl et al. 2015).

Germline pathogenic variants causing primary aldosteronism with autosomal dominant inheritance have been found in the CYP11B2, KCNJ5, CACNA1D and CACNA1H genes (Dutta et al. 2016; Mulatero et al. 2013).

To date, only a very limited number of germline missense changes have been found in CACNA1H in patients with primary aldosteronism (Scholl et al. 2015). CACNA1H encodes the α1 subunit of the T-type voltage calcium channel.

Scholl et al. performed exome sequencing in 40 unrelated individuals with hypertension due to primary aldosteronism with onset age by 10 years (Scholl et al. 2015). In these patients who were negative for pathogenic variants in the CYP11B2, KCNJ5, and CACNA1D genes, five probands were found to have a heterozygous missense pathogenic variant in the CACNA1H gene.

This test provides full coverage of all coding exons of the CACNA1H gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.