Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency

BMC Endocrine Disorders

Anke Tönjes¹  Peter Kovacs¹  Dagmar Führer³  Michael Stumvoll⁴  Dorit Schleinitz⁴  Kerstin Weidle⁴  Kerstin Krause⁴  Roland Pfäffle²  Marina Schlicke²  Jürgen Klammt²  Susanne Martens¹  Jana Breitfeld¹ 

[1] IFB Adiposity Diseases, University of Leipzig, Philipp-Rosenthal-Str. 27, Leipzig 04103, Germany;Hospital for Children & Adolescents, University of Leipzig, Liebigstrasse 22, Leipzig 04103, Germany;Department of Endocrinology, University of Essen, Hufelandstraße 55, Essen 45147, Germany;Department of Medicine, University of Leipzig, Liebigstrasse 20, Leipzig 04103, Germany

关键词: BMP7;    BMP4;    BMP2;    Bone morphogenetic proteins;    Combined pituitary hormone deficiency;   

Others  :  1085469
DOI  :  10.1186/1472-6823-13-56

 received in 2013-04-10, accepted in 2013-10-28,  发布年份 2013

【 摘 要 】

Background

The complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD.

Methods

We sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure.

Results

Sequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools.

Conclusions

A mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD.

【 授权许可】

   
2013 Breitfeld et al.; licensee BioMed Central Ltd.

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