Analysis of the insulin-like growth factor 1 receptor gene in children born small for gestational age: in vitro characterization of a novel mutation (p.Arg511Trp)

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP LEAL, Andrea C. FMUSP-HC
JORGE, Alexander A. L. FMUSP-HC 2013
dc.identifier.citation CLINICAL ENDOCRINOLOGY, v.78, n.4, p.558-563, 2013
dc.identifier.issn 0300-0664
dc.description.abstract Background Insulin-like growth factor 1 insensitivity caused by IGF1R mutations has been previously identified as one of the causes of growth impairment in children born small for gestational age (SGA). Objective To analyse the IGF1R in children born SGA. Subjects From an initial cohort of 54 sequential children born SGA, without catch-up growth, 25 children were selected for this IGF1R study due to the presence of serum IGF-1 values above the mean for their age and sex. Methods The proximal IGF1R promoter region, the entire coding region and the exonintron boundaries were directly sequenced, and multiplex ligation-dependent probe amplification analysis was performed. Fibroblast cultures were developed from one patient with a mutation for the in vitro characterization of IGF-1 insensitivity. Results The copy number variation analysis did not identify deletions involving the IGF1R gene. We identified two children carrying heterozygous nucleotide substitutions in IGF1R: c.16G>A/p.Gly6Arg and c.1531C>T/p.Arg511Trp. The first variant (p.Gly6Arg) was identified in control subjects (0 center dot 3%) and in a relative with normal growth; thus, it was considered to be a rare benign allelic variation. The second variant (p.Arg511Trp) was not found in 306 alleles from control subjects, and it segregated with the growth impairment phenotype in the patient's family. Fibroblasts obtained from this patient had a significantly reduced proliferative response and AKT phosphorylation after IGF-1 stimulation compared with control fibroblasts. Conclusion The identification of an inactivating IGF1R mutation in the present cohort should encourage further studies of larger series to establish the precise frequency of this molecular defect in children with growth impairment of a prenatal onset.
dc.description.sponsorship · Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [08/57915-2]
· Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [142062/06-5, 301339/2008-9, 300938/06-3, 475870/2009-3, 301477/2009-4]
dc.language.iso eng
dc.publisher WILEY-BLACKWELL
dc.relation.ispartof Clinical Endocrinology
dc.rights restrictedAccess
dc.subject.other short-stature; missense mutation; intrauterine; retardation; igf1r
dc.title Analysis of the insulin-like growth factor 1 receptor gene in children born small for gestational age: in vitro characterization of a novel mutation (p.Arg511Trp)
dc.type article
dc.rights.holder Copyright WILEY-BLACKWELL LIM/42 LIM/25 LIM/24
dc.identifier.doi 10.1111/cen.12048
dc.identifier.pmid 22998174
dc.type.category original article
dc.type.version publishedVersion LEAL, Andrea C.:FM: MONTENEGRO, Luciana R.:FM:MCM SAITO, Renata F.:FM: RIBEIRO, Tamaya C.:FM: MENDONCA, Berenice B.:FM:MCM ARNHOLD, Ivo J. P.:HC:ICHC JORGE, Alexander A. L.:FM:MCM · COUTINHO, Debora C.:Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM 42,Hosp Clin, Unidade Endocrinol Desenvolvimento,Disciplina End, BR-01246903 Sao Paulo, Brazil 2-s2.0-84875141087 WOS:000316229400013 HOBOKEN USA
hcfmusp.relation.reference · Abuzzahab MJ, 2003, NEW ENGL J MED, V349, P2211, DOI 10.1056/NEJMoa010107
· Adams TE, 2000, CELL MOL LIFE SCI, V57, P1050, DOI 10.1007/PL00000744
· Clayton PE, 2007, J CLIN ENDOCR METAB, V92, P804, DOI 10.1210/jc.2006-2017
· Coutinho DC, 2007, J CLIN ENDOCR METAB, V92, P4889, DOI 10.1210/jc.2007-1661
· DECHIARA TM, 1990, NATURE, V345, P78, DOI 10.1038/345078a0
· Ester WA, 2009, J CLIN ENDOCR METAB, V94, P4717, DOI 10.1210/jc.2008-1502
· Fang P, 2012, J CLIN ENDOCR METAB, V97, pE243, DOI 10.1210/jc.2011-2142
· Fang P, 2009, J CLIN ENDOCR METAB, V94, P1740, DOI 10.1210/jc.2008-1903
· Inagaki K, 2007, J CLIN ENDOCR METAB, V92, P1542, DOI 10.1210/jc.2006-2354
· Kawashima Y, 2005, J CLIN ENDOCR METAB, V90, P4679, DOI 10.1210/jc.2004-1947
· Kawashima Y, 2012, CLIN ENDOCRINOL, V77, P246, DOI 10.1111/j.1365-2265.2012.04357.x
· Kruis T, 2010, J CLIN ENDOCR METAB, V95, P1137, DOI 10.1210/jc.2009-1433
· Leal AD, 2011, ARQ BRAS ENDOCRINOL, V55, P541, DOI 10.1590/S0004-27302011000800007
· Mohn A, 2011, HORM RES PAEDIAT, V76, P136, DOI 10.1159/000324957
· Montenegro LR, 2012, EUR J ENDOCRINOL, V166, P543, DOI 10.1530/EJE-11-0964
· Raile K, 2006, J CLIN ENDOCR METAB, V91, P2264, DOI 10.1210/jc.2005-2146
· Schwarz JM, 2010, NAT METHODS, V7, P575, DOI 10.1038/nmeth0810-575
· TADA H, 1986, J IMMUNOL METHODS, V93, P157, DOI 10.1016/0022-1759(86)90183-3
· TANNER JM, 1966, ARCH DIS CHILD, V41, P454
· Walenkamp MJE, 2006, J CLIN ENDOCR METAB, V91, P3062, DOI 10.1210/jc.2005-1597
· Wallborn T, 2010, J CLIN ENDOCR METAB, V95, P2316, DOI 10.1210/jc.2009-2404
· Woods KA, 1996, NEW ENGL J MED, V335, P1363, DOI 10.1056/NEJM199610313351805
dc.description.index MEDLINE
hcfmusp.citation.scopus 10
hcfmusp.citation.wos 11 Brasil

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