We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Familial Isolated Primary Pigmented Nodular Adrenocortical Disease Associated with a Novel Low Penetrance PRKAR1A Gene Splice Site Mutation.
- Authors
Storr, Helen L.; Metherell, Louise A.; Dias, Renuka; Savage, Martin O.; Rasmussen, Åse K.; Clark, Adrian J.L.; Main, Katharina M.
- Abstract
Background/Aims: Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating germline protein kinase A regulatory subunit type 1-α (PRKAR1A) mutations and loss of heterozygosity at the 17q22-24 locus in approximately 50% patients. PRKAR1A mutations are observed in both isolated PPNAD (iPPNAD) and Carney complex (CNC). Most mutations result in a functionally null-allele and exhibit high penetrance. We genotyped members of an extended family for a novel PRKAR1A mutation and undertook detailed phenotyping for CNC in the affected individuals. Methods: A 10.5-year-old male was diagnosed with PPNAD; the patient's mother also had iPPNAD. A 13-year-old sibling and 7 other relatives (mean age 58.2, range 29.1-80.2 years) were referred for PRKAR1A mutation analysis. Results: DNA analysis of the index case and parent revealed a novel germline heterozygous PRKAR1A mutation at the +1 position of the acceptor site of intron 3 [c.349 G>T]. The same heterozygous splice site mutation was present in the sibling with no PPNAD or CNC manifestations and 2 other individuals aged 54.9 and 57.1 years who had subclinical Cushing's syndrome but no features of CNC. Conclusion: We conclude that c.349 G>T, a novel splice site germline PRKAR1A defect, has low penetrance resulting in incomplete clinical expression in this kindred. Copyright © 2010 S. Karger AG, Basel
- Subjects
GENETIC research; NODULAR disease; GERM cells; PROTEIN kinases; PHENOTYPES; RNA splicing; CUSHING'S syndrome
- Publication
Hormone Research in Paediatrics, 2010, Vol 73, Issue 2, p115
- ISSN
1663-2818
- Publication type
Article
- DOI
10.1159/000277629