Systematic screening for PRKAR1A gene rearrangement in Carney complex: identification and functional characterization of a new in-frame deletion.
Eur J Endocrinol
; 170(1): 151-160, 2014 Jan.
Article
in En
| MEDLINE
| ID: mdl-24144965
ABSTRACT
BACKGROUND:
Point mutations of the PRKAR1A gene are a genetic cause of Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), but in 30% of the patients no mutation is detected.OBJECTIVE:
Set up a routine-based technique for systematic detection of large deletions or duplications of this gene and functionally characterize these mutations.METHODS:
Multiplex ligation-dependent probe amplification (MLPA) of the 12 exons of the PRKAR1A gene was validated and used to detect large rearrangements in 13 typical CNC and 39 confirmed or putative PPNAD without any mutations of the gene. An in-frame deletion was characterized by western blot and bioluminescence resonant energy transfer technique for its interaction with the catalytic subunit.RESULTS:
MLPA allowed identification of exons 3-6 deletion in three patients of a family with typical CNC. The truncated protein is expressed, but rapidly degraded, and does not interact with the protein kinase A catalytic subunit.CONCLUSIONS:
MLPA is a powerful technique that may be used following the lack of mutations detected by direct sequencing in patients with bona fide CNC or PPNAD. We report here one such new deletion, as an example. However, these gene defects are not a frequent cause of CNC or PPNAD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Rearrangement
/
Gene Deletion
/
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
/
Carney Complex
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Eur J Endocrinol
Journal subject:
ENDOCRINOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
France
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM