ECE2014 Poster Presentations Adrenal cortex (56 abstracts)
A three generation family with low cortisol, CBG deficiency, chronic fatigue and pain, lipomatosis and behavioral alterations
Stefania Moia 1 , Gillian Elisabeth Walker 1 , Marta Roccio 1 , Roberta Ricotti 1 , Enza Giglione 1 , Simonetta Bellone 1 , Flaminia Fanelli 2 , Gianni Bona 1 & Flavia Prodam 1
1Dipartimento di Scienze della Salute, Università del Piemonte Orientale A. Avogadro, Novara, Italy; 2Dipartimento di Medicina Clinica U.O., Endocrinologia Policlinico S. Orsola-Malpighi, Bologna, Italy.
Introduction: CBG is the main transport protein for glucocorticoids in blood. CBG gene is a member of the serine protease inhibitor family, located at chromosome 14q32. Inherited CBG deficiency (MIM 611489) is a rarely recessive disorder, and the phenotype associated includes low cortisol levels, presence of normal ACTH levels, hypotension and fatigue, although the exact pathophysiological mechanisms involved remain uncertain. We identified a family with a complex phenotype, that includes low free cortisol levels, lipomatosis, chronic fatigue, pain and CBG deficiency, with a segregation suggestive of a monogenic inheritance. Aim of the study is to explore which gene is involved in this complex disease suggestive to be hereditary.
Description of methods/design: We quantified the plasmatic concentration of CBG protein both in our family (n=9) than in a group of healthy controls (n=15) by using a commercial kit. Molecular analysis of four coding exons of CBG gene was performed by direct sequencing. Segregation analysis of parental alleles was performed through linkage analysis.
Results: Salivary and LC–MS/MS analysis identified very low free cortisol levels in two childrens and in the father, despite normal ACTH levels, with cortisol levels at the end of normal range in the sister and paternal grandfather. The maternal grandfather, the father and the two male children presented low plasmatic CBG levels. Paternal grandfather presented CBG levels at the end of the normal range. No mutations were identified in the CBG gene coding-regions. We identified only five SNPs. Linkage analysis identified a likely paternal transmission of the CBG alleles.
Conclusion: With the hypothesis that our family is affected by inherited CBG deficiency, molecular analysis of non-coding regions and functional studies of CBG gene will be performed. In addition, the involvement of supplementary gene-disease will be demonstrated by cGH array and exome sequencing analysis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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