@article{c55ed08bf3864a2ab49a255b3650d5f8,
title = "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{\textquoteright}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{\textquoteright}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.",
keywords = "Carney complex, PRKAR1A, SNP array, deletion of a promoter",
author = "Shin Ito and Aya Hashimoto and Kazunori Yamaguchi and Sadafumi Kawamura and Shingo Myoen and Maki Ogawa and Ikuro Sato and Takamichi Minato and Shingo Miyabe and Akira Nakazato and Keitaro Fujii and Mai Mochizuki and Haruna Fujimori and Keiichi Tamai and Tetsuya Niihori and Yoko Aoki and Akira Sugawara and Hironobu Sasano and Hiroshi Shima and Jun Yasuda",
note = "Funding Information: The authors thank Mr. Tetsuhiro Moriya for his advice on the SNP array data analyses and Ms. Mika Takeuchi for her support regarding CGP data acquisition. They also thank Michelle Kahmeyer‐Gabbe, PhD, from Edanz Group ( https://en‐author‐services.edanzgroup.com/ ) for editing a draft of this manuscript. This work was supported by JSPS KAKENHI with following grant numbers: JP17K07187 (to H. Shima), JP19K08430 (to K. Tamai), JP18K09363 (to M. Mochizuki), JP21K15495 (to H. Fujimori), and JP17K07193 (to J. Yasuda). This work was also supported by the Foundation for the Promotion of Cancer Research in Japan, Takeda Medical Foundation, and Kobayashi Foundation for Cancer Research (K. Tamai). JY, SK, TN, and HS planned the study. S. Myoen, MO, AS, and JY collected clinical data. IS and HS contributed the histopathologic examination. SI, AH, KY, AN, KF, MM performed experiments. TM, SM, HF, KT, and HS prepared essential materials for experiment. SI, HF, YA, and JY wrote the manuscript. SK, KT, and HS performed critical reading of the draft manuscript. Publisher Copyright: {\textcopyright} 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.",
year = "2022",
month = mar,
doi = "10.1002/mgg3.1884",
language = "English",
volume = "10",
journal = "Molecular genetics & genomic medicine",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",
number = "3",
}
