Identification of novel genetic variants in phosphodiesterase 8B ( PDE8B ), a cAMP-specific phosphodiesterase highly expressed in the adrenal cortex, in a cohort of patients with adrenal tumours

被引：62

作者：

Rothenbuhler, Anya ^{[1
,2
]}

Horvath, Anelia ^{[1
,2
]}

Libe, Rossella ^{[3
,4
,5
,6
]}

Faucz, Fabio R. ^{[1
,2
]}

Fratticci, Amato ^{[3
,4
]}

Sanson, Marie L. Raffin ^{[3
,4
,7
]}

Vezzosi, Delphine ^{[3
,4
]}

Azevedo, Monalisa ^{[1
,2
]}

Levy, Isaak ^{[2
]}

Almeida, Madson Q. ^{[1
,2
]}

Lodish, Maya ^{[1
,2
]}

Nesterova, Maria ^{[1
,2
]}

Bertherat, Jerome ^{[3
,4
,5
,6
]}

Stratakis, Constantine A. ^{[1
,2
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Sect, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA

[2] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Genet & Pediat Endocrinol Training Program, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA

[3] CNRS, INSERM, U1016, Metab & Canc Inst,Dept Endocrinol,UMR 8104, F-75700 Paris, France

[4] Univ Paris Descartes Paris, Paris, France

[5] Hop Cochin, AP HP, Dept Endocrinol, Ctr Rare Adrenal Dis, Paris, France

[6] INCa Comete Network Adrenal Canc, Paris, France

[7] Hop Ambroise Pare, AP HP, Boulogne, France

来源：

CLINICAL ENDOCRINOLOGY | 2012年 / 77卷 / 02期

基金：

美国国家卫生研究院;

关键词：

REGULATORY SUBUNIT; MUTATIONS; PDE11A; 11A; HYPERPLASIA;

D O I：

10.1111/j.1365-2265.2012.04366.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumours. Mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions. Objective To screen for genetic variations in PDE8B among patients with different types of adrenocortical tumours. Design and subjects This is a casecontrol study followed by functional analyses. Two hundred and sixteen unrelated patients with different types of adrenocortical tumours and 192 healthy control individuals participated in the study. Methods Bidirectional Sanger sequencing, in vitro cell line transfection and in silico modelling are used in this study. Results Nine different PDE8B sequence changes, six novel and three previously reported, were identified in our patients and controls. Two of the variations, seen only in the patient group, showed significant potential to impair protein function, both in vitro and in silico. Conclusion PDE8B is another PDE gene in which variations may contribute to predisposition of adrenocortical tumours.

引用

页码：195 / 199

页数：5

共 16 条

[11] Functional Phosphodiesterase 11A Mutations May Modify the Risk of Familial and Bilateral Testicular Germ Cell Tumors [J].