Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism. (6th February 2015)

• Record Type: Journal Article
• Authors: Fritez, Nabila; Sobrier, Marie‐Laure; Iraqi, Hinde; Vié‐Luton, Marie‐Pierre; Netchine, Irène; El Annas, Abdessamad; Pantel, Jacques; Collot, Nathalie; Rose, Sophie; Piterboth, William; Legendre, Marie; Chraibi, Abdelmjid; Amselem, Serge; Kadiri, Abdelkrim; Hilal, Latifa
• Is Part Of: Clinical endocrinology. Volume 82:Number 6(2015:Jun.)
• Page Start: 876
• Page End: 884
• Publication Date: 2015-02-06
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12706
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12706-abs-0001"> <title>Summary</title> <sec id="cen12706-sec-0001" sec-type="section"> <title>Background/Objectives</title> <p>Congenital hypopituitarism is a rare disease which, for most patients, has no identified molecular cause. We aimed to document the molecular basis of growth retardation in a Moroccan cohort.</p> </sec> <sec id="cen12706-sec-0002" sec-type="section"> <title>Design/Patients</title> <p>80 index cases [54 with isolated growth hormone deficiency (IGHD), 26 with combined pituitary hormone deficiency (CPHD)] were screened for molecular defects in <italic>GH1</italic> (including <italic>LCR‐GH1)</italic>, <italic> GHRHR</italic>, <italic> GHSR</italic>, <italic> GHRH</italic>, <italic> PROP1</italic>, <italic> POU1F1</italic>, <italic> HESX1</italic>, <italic> LHX3</italic>, <italic> LHX4</italic> and <italic>SOX3</italic>.</p> </sec> <sec id="cen12706-sec-0003" sec-type="section"> <title>Results</title> <p>Five different deleterious mutations were identified in 14 patients from eight families. In the IGHD group, three genes were found to be involved: <italic>GH1</italic>, <italic> GHRHR</italic> and <italic>GHSR</italic>. In the CPHD group, <italic>PROP1</italic> was the only mutated gene. In addition, two heterozygous variations whose deleterious effect remains to be demonstrated were identified (in <italic>GH1</italic> and <italic>LHX4</italic>), and two polymorphisms (missense variations) were detected (in <italic>LHX3</italic> and in <italic>GHSR</italic>). The prevalence of mutations in this Moroccan GHD cohort was 10% (8/80), 11·1% (6/54) in the IGHD group and 7·7% (2/26) in the CPHD group.</p> </sec> <sec id="cen12706-sec-0004" sec-type="section"> <title>Conclusion</title> <p>This is the first molecular screening of congenital GHD in a Moroccan population and, like other studies, mutations were preferentially identified in familial cases (75%); mutations in genes such as <italic>POU1F1</italic>, <italic> HESX1</italic>, <italic> SOX3</italic>, <italic> LHX3</italic> and <italic>LHX4</italic> are extremely rare. The p.R73C <italic>PROP1</italic> mutation was the most frequent mutation in CPHD; this should be the first one to screen in this population. Our results should contribute to a better diagnosis and management of this heterogeneous disease condition.</p> </sec> </abstract>