title: A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney Complex Family.
abstract: BACKGROUND
  Carney complex (CNC) is an autosomal dominant inherited disease, characterized by spotty skin pigmentation, cardiac and cutaneous myxomas, and endocrine overactivity. We report on a Chinese CNC family with a novel mutation in the protein kinase A regulatory subunit 1 (PRKAR1A) gene.
  
  
  METHODS
  Target-exome sequencing was performed to identify the mutation of PRKAR1A in 2 members of the CNC family.
  
  
  RESULTS
  The proband was a young man with typical CNC, including pigmentation, cutaneous myxomas, cardiac myxoma, Sertoli cell tumour of his left testis, and multiple hypoechoic thyroid nodules. His mother also had CNC with skin pigmentation, cutaneous myxomas, and a cardiac myxoma. Target-exome capture analysis revealed that the proband and the mother carried a novel heterozygous mutation in the exon 6 splicing donor site of PRKAR1A. Sequencing analysis of myxoma messenger RNA revealed that the mutation abrogated exon 6 preRNA splicing, leading to a frameshift starting at Valine 185 and premature translation termination in intron 6. The truncated enzyme lacks the functional cyclic adenosine monophosphate (cAMP) binding domain at the C-terminus, causing PRKAR1A haploinsufficiency.
  
  
  CONCLUSIONS
  In this study we report on a novel splicing mutation in the PRKAR1A gene that adds to the genetic heterogeneity of CNC.
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Changchun, Jilin, China; Department of Cardiac Surgery, First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Changchun, Jilin, China. Electronic address: chenx@jlu.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cancer and Stem Cell Center, First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Jingnan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Cancer and Stem Cell Center, First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Cardiac Surgery, First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Ultrasonic Cardiogram, First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.affiliation: Cancer and Stem Cell Center, First Hospital of Jilin University, Changchun, Jilin, China; Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, California, USA. Electronic address: Jifan@stanford.edu.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Department of Cardiac Surgery, First Hospital of Jilin University, Changchun, Jilin, China. Electronic address: gaoyongsheng1964@163.com.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D056733:Carney Complex / Q000235:genetics* / Q000378:metabolism; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D012322:RNA Precursors; D055815:Young Adult
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D012322:RNA Precursors; D012313:RNA