A novel 8.57-kb deletion of the upstream region of PRKAR1A in a family with Carney complex.

Abstract

Carney complex (CNC) is a rare hereditary syndrome that involves endocrine dysfunction and the development of various types of tumors. Chromosome 2p16 and PRKAR1A on chromosome 17 are known susceptibility loci for CNC. Here we report a mother and son with CNC caused by an 8.57-kb deletion involving the transcription start site and non-coding exon 1 of PRKAR1A. The proband is a 28-year-old male with bilateral large-cell calcified Sertoli cell testicular tumors and pituitary adenoma. Comprehensive genomic profiling for cancer mutations using Foundation One CDx failed to detect any mutations in PRKAR1A in DNA from the testicular tumor. Single-nucleotide polymorphism array analysis of the proband's genomic DNA revealed a large deletion in the 5' region of PRKAR1A. Genomic walking further delineated the region an 8.57-kb deletion. A 1.68-kb DNA fragment encompassed by the deleted region showed strong promoter activity in a NanoLuc luciferase reporter assay. The patient's mother, who is suffering from recurrent cardiac myxoma, a critical sign for CNC, carried an identical deletion. The 8.57-kb deleted region is a novel lesion for CNC and will facilitate molecular diagnosis of the disease.

• Authors: Shin Ito, Aya Hashimoto, Kazunori Yamaguchi, Sadafumi Kawamura, Shingo Myoen, Maki Ogawa, Ikuro Sato, Takamichi Minato, Shingo Miyabe, Akira Nakazato, Keitaro Fujii, Mai Mochizuki, Haruna Fujimori, Keiichi Tamai, Tetsuya Niihori, Yoko Aoki, Akira Sugawara, Hironobu Sasano, Hiroshi Shima, Jun Yasuda
• Journal: Molecular genetics & genomic medicine (Mol Genet Genomic Med) Vol. 10 Issue 3 Pg. e1884 (03 2022) ISSN: 2324-9269 [Electronic] United States
• PMID: 35128829 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Chemical References

• Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
• PRKAR1A protein, human
• Luciferases
• nanoluc

Topics

• Adult
• Carney Complex (diagnosis, genetics, pathology)
• Cyclic AMP-Dependent Protein Kinase RIalpha Subunit (genetics)
• Exons
• Humans
• Luciferases
• Male
• Myxoma (genetics, pathology)