ECE2007 Poster Presentations (1) (659 abstracts)
Idiopathic isolated GH deficiency (IGHD) and combined pituitary hormone deficiency (CPHD) in Italy: genetic screening and clinical correlates
Ginevra Corneli 1 , Daniela Vivenza 1 , Simona Mellone 2 , Luigi Tiradani 2 , Yari Carlomagno 2 , Michela Godi 2 , Simonetta Bellone 1 , Gianluca Aimaretti 3 , Mara Giordano 2 , Patricia Momigliano-Richiardi 2 & Gianni Bona 1
1Unit of Paediatrics, Department of Medical Sciences, University of Piemonte Orientale “Amedeo Avogadro”, Novara, Italy; 2Laboratory of Human Genetics, Department of Medical Sciences, University of Piemonte Orientale “Amedeo Avogadro”, Novara, Italy; 3Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale “Amedeo Avogadro”, Novara, Italy.
Mutations in genes encoding pituitary-specific factors have been identified in patients with idiopathic isolated GH deficiency (IGHD) or combined pituitary hormone deficiency (CPHD), with or without neuro-morphological abnormalities. We screened 205 IGHD (M/F:131/74; 183 sporadic and 22 belonging to 12 families) for mutations in GH1, GHRH-R, HESX1 and 129 CPHD, (M/F:75/54; 118 sporadic and 13 belonging to 9 families) for mutations in PIT1, PROP1, LHX4 and HESX1. We considered as familial cases both patients with family history of the disease and those with consanguineous parents. All the CPHD patients had GH deficiency. All IGHD were diagnosed during childhood. Among CPHD patients 82 were diagnosed in childhood, 14 during adolescence and 33 in adulthood. Neuroradiological abnormalities at MRI scan were found in 26.8% of IGHD and 65.1% of CPHD. Mutations were detected in the GH1 gene in two IGHD familial cases (a homozygous tandem duplication within exon 2 and a heterozygous IVSdel+56–77) and in two CPHD familial cases, one in PIT1 (IVS2+3insA heterozygote) and one in PROP1 (R73C/R73H compound heterozygote). Among sporadic cases likely causal mutations were identified in one IGHD in HESX1 (IVS2+3G→A heterozygote) and in three CPHD, of which two in PROP1 (296delGA and 150delA, both in homozygosis) and one in HESX1 (Q6H heterozygote). No mutations were found in the LHX4 gene. Thus, we found mutations in 4 out of 21 families (19%) and 4 out of 301 sporadic cases (1,3%). In four further sporadic cases sequence variations were detected (one V10G in GHRH-R and three V129I in HESX1) but there is still no evidence of their pathogenic role. In conclusion, most causal mutations in the genes analysed in this study were found in familial cases. Thus, the inclusion criteria for the genetic analysis, at least for sporadic patients, should be better clarified, prior to offering genetic testing.
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