# New mutation of CACNA1H p.Tyr613Phe in hyperaldosteronism: a case report

## TL;DR

A new mutation in the CACNA1H gene is linked to hyperaldosteronism, expanding understanding of the genetic causes of this condition.

## Contribution

The study identifies a novel germline CACNA1H mutation (p.Tyr613Phe) associated with primary aldosteronism.

## Key findings

- A patient with unilateral adrenal hyperplasia was found to have CACNA1H mutations confirmed by sequencing.
- The p.Tyr613Phe variant is located in a highly conserved region of the protein and is predicted to be damaging.
- The findings suggest a broader genetic spectrum for primary aldosteronism and highlight the role of genetic testing.

## Abstract

Primary aldosteronism (PA) is an endocrine disorder characterized by the autonomous, excessive production of aldosterone from the adrenal glands. Familial hyperaldosteronism (FH) is one type of PA. FH is further subclassified into types I through IV according to different gene mutations.

This paper reports a case of unilateral adrenal hyperplasia with germline CACNA1H mutation, p.His515Tyr and p.Tyr613Phe, confirmed by endocrine test, whole exome sequencing and Sanger sequencing 4 years after onset. The variants located within N-terminal close to the first transmembrane domain of the protein that was highly conserved across different species. Polyphen2 and PROVEAN predicted p.Tyr613Phe to be probably damaging and deleterious.

These findings broaden the genetic spectrum of PA and offer novel insights into the molecular mechanisms driving excessive aldosterone production. Therefore, genetic sequencing is recommended for PA patients whose etiology remains unclear after standard clinical evaluation.