E Inzaghi1, A Deodati2, S Loddo3, M Mucciolo3, F Verdecchia2, E Sallicandro3, G Catino3, M Cappa2, A Novelli3, S Cianfarani2,4,5. 1. Dipartimento Pediatrico Universitario Ospedaliero, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy. elena.inzaghi@opbg.net. 2. Dipartimento Pediatrico Universitario Ospedaliero, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy. 3. Translational Cytogenomics Research Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy. 4. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 5. Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
Abstract
PURPOSE: Multiple factors influence intrauterine growth and lead to low birth sizes. The impact of genetic alterations on both pre- and post-natal growth is still largely unknown. The aim of this study was to investigate the prevalence of CNVs in an Italian cohort of SGA children with persistent short stature and complex clinical phenotype. rhGH treatment efficacy was evaluated according to the different genotypes. SUBJECTS AND METHODS: Twenty-four SGA children (10F/14M) with persistent short stature associated with dysmorphic features and/or developmental delay underwent CNV evaluation. RESULTS: CNVs were present in 14/24 (58%) SGA children. Six patients had a microdeletion involving the following regions: 3q24q25.1, 8p21.2p12, 15q26, 19q13.11, 20q11.21q12, 22q11.2. In three females, the same microdeletion involving 17p13.3 region was identified. In two different patients, two microduplications involving 10q21.3 and Xp11.3 region were observed. A further female patient showed both an 11q12.1 and an Xq27.1 microduplication, inherited from her mother and from her father, respectively. In a boy, the presence of a 12p13.33 microdeletion and a 19q13.43 microduplication was found. GH treatment efficacy, expressed by height gain and height velocity in the first 12 months of therapy, was similar in subjects with and without CNVs. CONCLUSIONS: These results show that pathogenic CNVs are common in SGA children with short stature associated with additional clinical features. Interestingly, the involvement of 17p13.3 region occurs with a relative high frequency, suggesting that genes located in this region could play a key role in pre- and post-natal growth. rhGH therapy has similar efficacy in the short term whether CNVs are present or not.
PURPOSE: Multiple factors influence intrauterine growth and lead to low birth sizes. The impact of genetic alterations on both pre- and post-natal growth is still largely unknown. The aim of this study was to investigate the prevalence of CNVs in an Italian cohort of SGA children with persistent short stature and complex clinical phenotype. rhGH treatment efficacy was evaluated according to the different genotypes. SUBJECTS AND METHODS: Twenty-four SGA children (10F/14M) with persistent short stature associated with dysmorphic features and/or developmental delay underwent CNV evaluation. RESULTS: CNVs were present in 14/24 (58%) SGA children. Six patients had a microdeletion involving the following regions: 3q24q25.1, 8p21.2p12, 15q26, 19q13.11, 20q11.21q12, 22q11.2. In three females, the same microdeletion involving 17p13.3 region was identified. In two different patients, two microduplications involving 10q21.3 and Xp11.3 region were observed. A further female patient showed both an 11q12.1 and an Xq27.1 microduplication, inherited from her mother and from her father, respectively. In a boy, the presence of a 12p13.33 microdeletion and a 19q13.43 microduplication was found. GH treatment efficacy, expressed by height gain and height velocity in the first 12 months of therapy, was similar in subjects with and without CNVs. CONCLUSIONS: These results show that pathogenic CNVs are common in SGA children with short stature associated with additional clinical features. Interestingly, the involvement of 17p13.3 region occurs with a relative high frequency, suggesting that genes located in this region could play a key role in pre- and post-natal growth. rhGH therapy has similar efficacy in the short term whether CNVs are present or not.
Authors: Astrid Lunde; Kari Klungsøyr Melve; Håkon K Gjessing; Rolv Skjaerven; Lorentz M Irgens Journal: Am J Epidemiol Date: 2007-02-20 Impact factor: 4.897
Authors: P E Clayton; S Cianfarani; P Czernichow; G Johannsson; R Rapaport; A Rogol Journal: J Clin Endocrinol Metab Date: 2007-01-02 Impact factor: 5.958
Authors: David T Miller; Margaret P Adam; Swaroop Aradhya; Leslie G Biesecker; Arthur R Brothman; Nigel P Carter; Deanna M Church; John A Crolla; Evan E Eichler; Charles J Epstein; W Andrew Faucett; Lars Feuk; Jan M Friedman; Ada Hamosh; Laird Jackson; Erin B Kaminsky; Klaas Kok; Ian D Krantz; Robert M Kuhn; Charles Lee; James M Ostell; Carla Rosenberg; Stephen W Scherer; Nancy B Spinner; Dimitri J Stavropoulos; James H Tepperberg; Erik C Thorland; Joris R Vermeesch; Darrel J Waggoner; Michael S Watson; Christa Lese Martin; David H Ledbetter Journal: Am J Hum Genet Date: 2010-05-14 Impact factor: 11.025
Authors: Susanne E Stalman; Nita Solanky; Miho Ishida; Cristina Alemán-Charlet; Sayeda Abu-Amero; Marielle Alders; Lucas Alvizi; William Baird; Charalambos Demetriou; Peter Henneman; Chela James; Lia C Knegt; Lydia J Leon; Marcel M A M Mannens; Adi N Mul; Nicole A Nibbering; Emma Peskett; Faisal I Rezwan; Carrie Ris-Stalpers; Joris A M van der Post; Gerdine A Kamp; Frans B Plötz; Jan M Wit; Philip Stanier; Gudrun E Moore; Raoul C Hennekam Journal: J Clin Endocrinol Metab Date: 2018-03-01 Impact factor: 5.958