ECE2014 Poster Presentations Developmental Endocrinology (6 abstracts)
Genome-wide survey for clinically relevant structural abnormalities contributing to pathogenesis of combined pituitary hormone deficiency (CPHD) with childhood onset.
Bartlomiej Budny 1 , Malgorzata Rydzanicz 2 , Klaudia Szymczak 1 , Małgorzata Szkudlarek 1 , Kosma Woliński 1 , Elzbieta Wrotkowska 1 , Daria Baszko-Błaszyk 1 , Monika Gołęb 1 , Tomasz Bednarczuk 3 , Urszula Ambroziak 3 , Marek Niedziela 4 , Monika Obara-Moszyńska 4 , Barbara Rabska 4 , Natalia Derebecka 5 , Hans Bluijssen 2 , Joanna Wesoły 5 , Marek Ruchała 1 & Katarzyna Ziemnicka 1
1Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland; 2Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznań, Poland; 3Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland; 4Department of Paediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznań, Poland; 5Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznań, Poland.
Introduction: Combined pituitary hormone deficiency (CPHD) results in deficit of growth hormone and coexisting failure of synthesis or excretion at least another pituitary hormone. Transcription factors controlling expression of genes required for pituitary organogenesis are orchestrating entire development process and certain cell lineages differentiation, contributing therefore significantly to CPHD pathogenesis with childhood onset.
Aims: The purpose of the study was a genome-wide screening using microarrays for novel factors controlling pituitary organogenesis (genes, CNV), and contributing to combined pituitary hormone deficiency (CPHD).
Methods: The entire CPHD cohort of patients consist of 102 individuals. All patients were screened for mutations and copy number of known pituitary related genes (PROP1, POU1F1, HESX1, LHX3 and LHX4) using sequencing and MLPA. Fifty-six patients without identified alterations were screened for genomic imbalances employing microarray technology (Illumina, Affymetrix). Genomic size of CNVs, their location, clinical significance and encompassing genes were thoroughly examined. Parental studies were conducted to determine pathogenic CNVs and the inheritance in a subset of cases where parental samples were referred for follow-up testing.
Results: Among genomic changes we identified recurrence of deletions and duplications. Further examination revealed presence of genes playing a role in pituitary functioning (i.e. PPYR1) or transcriptional regulators (ZNF826, ZNF737). A cohort of CNVs shows overlap with clinically valid regions deposited in DECIPHER and ClinVar databases, and reporting complex clinical phenotypes including growth abnormalities.
Conclusions: Given the rapid expansion of efficient genomic technologies, examination of substantial group of CPHD patients will result in emerging novel interesting targets and determine significance of recurrent rare CNVs. This data will facilitate our understanding of complexity of pituitary processes and hopefully will support diagnosis, management, and care CPHD patients in the future.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more