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Eur J Endocrinol. 2013 Nov 29;170(1):151-160. doi: 10.1530/EJE-13-0740. Print 2014 Jan.

Systematic screening for PRKAR1A gene rearrangement in Carney complex: identification and functional characterization of a new in-frame deletion.

Author information

1
Département de Biologie Hormonale, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, 27 Rue du Faubourg Saint Jacques, 75014 Paris, France.
2
INSERM U970, Université Paris Descartes, PARCC, 56 Rue Leblanc, 75015 Paris, France.
3
Serviço de Genetica Medica, Departamento Pediatrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
4
Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK.
5
Service d'Endocrinologie, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, 75014 Paris, France.
6
Serviço de Endocrinologia.
7
Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
8
INSERM U1060, CNRS, Institut Cochin, Université Paris Descartes, Paris, France.
#
Contributed equally

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.

PMID:
24144965
PMCID:
PMC4733623
DOI:
10.1530/EJE-13-0740
[Indexed for MEDLINE]
Free PMC Article

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