A novel splice site mutation of the PRKAR1A gene, C.440 5 G > C, in a Chinese family with Carney complex

作者：Fu, J; Lai, F; Chen, Y; Wan, X; Wei, G; Li, Y; Xiao, H; Cao, X^*

来源：JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2018, 41(8): 909-917.

DOI：10.1007/s40618-017-0817-5

• Carney complex
• Primary pigmented nodular adrenocortical disease
• PRKAR1A gene mutation
• Splice site mutation
• Pedigree

Carney complex (CNC) is an extremely rare, multiple endocrine neoplasia syndrome that occurs in an autosomal dominant manner. Mutations in PRKAR1A have been reported to be a common genetic cause of CNC.
In this study, we reported a Chinese pedigree of CNC that manifests mainly as spotty skin pigmentation and primary pigmented nodular adrenocortical disease. Whole blood samples of this pedigree were collected for DNA/RNA analysis. Polymerase chain reaction (PCR) and reverse-transcription polymerase chain reaction analyses were performed to amplify the 11 exons and adjacent introns of PRKAR1A. Direct sequencing was used to detect the mutation, and DNA from 70 Han Chinese people was extracted and sequenced as a control to estimate the frequency of the identified mutation.
Within the pedigree, ten patients with CNC were identified, and a novel heterozygous mutation (c.440 5 G > C in intron 4a) was identified in the PRKAR1A gene. PCR amplification of cDNA from the control subjects and patients was performed. Agarose gel electrophoresis showed only one wild-type band in the cDNA corresponding to the former group, whereas an extra band was present in samples from the latter group corresponding to the skipping of exon 4a; this confirms that the variant affects PRKAR1A splicing.
In conclusion, the c.440 5 G > C mutation is a new splice site mutation that has not been reported and has the potential to broaden the mutational spectrum of PRKAR1A that is associated with CNC, which would facilitate genetic diagnosis and counseling for CNC.

• 出版日期2018-8
• 单位中山大学