Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations.

ABSTRACT:

Objective

We have recently reported five patients with bilateral adrenocortical hyperplasia (BAH) and Cushing's syndrome (CS) caused by constitutive activation of the catalytic subunit of protein kinase A (PRKACA). By doing new in-depth analysis of their cytogenetic abnormality, we attempted a better genotype-phenotype correlation of their PRKACA amplification.

Design

This study is a case series.

Methods

Molecular cytogenetic, genomic, clinical, and histopathological analyses were performed in five patients with CS.

Results

Reinvestigation of the defects of previously described patients by state-of-the-art molecular cytogenetics showed complex genomic rearrangements in the chromosome 19p13.2p13.12 locus, resulting in copy number gains encompassing the entire PR

SUBMITTER: Lodish MB 

PROVIDER: S-EPMC4428149 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature