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Breitfeld J, Martens S, Klammt J, et al. Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency. BMC Endocr Disord. 2013;13:56doi: 10.1186/1472-6823-13-56.
Breitfeld, J., Martens, S., Klammt, J., Schlicke, M., Pfäffle, R., Krause, K., Weidle, K., Schleinitz, D., Stumvoll, M., Führer, D., Kovacs, P., & Tönjes, A. (2013). Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency. BMC endocrine disorders, 1356. https://doi.org/10.1186/1472-6823-13-56
Breitfeld, Jana, et al. "Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency." BMC endocrine disorders vol. 13 (2013): 56. doi: https://doi.org/10.1186/1472-6823-13-56
Breitfeld J, Martens S, Klammt J, Schlicke M, Pfäffle R, Krause K, Weidle K, Schleinitz D, Stumvoll M, Führer D, Kovacs P, Tönjes A. Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency. BMC Endocr Disord. 2013 Dec 01;13:56. doi: 10.1186/1472-6823-13-56. PMID: 24289245; PMCID: PMC4175098.
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BMC Endocr Disord. 2013 Dec 01;13:56. doi: 10.1186/1472-6823-13-56.

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

BMC endocrine disorders

Jana Breitfeld, Susanne Martens, Jürgen Klammt, Marina Schlicke, Roland Pfäffle, Kerstin Krause, Kerstin Weidle, Dorit Schleinitz, Michael Stumvoll, Dagmar Führer, Peter Kovacs, Anke Tönjes

Affiliations

  1. Department of Medicine, University of Leipzig, Liebigstrasse 20, Leipzig 04103, Germany. [email protected].

PMID: 24289245 PMCID: PMC4175098 DOI: 10.1186/1472-6823-13-56

Abstract

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.

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