000168469 001__ 168469
000168469 005__ 20260210085434.0
000168469 0247_ $$2doi$$a10.1111/j.1365-2265.2012.04481.x
000168469 0248_ $$2sideral$$a81190
000168469 037__ $$aART-2013-81190
000168469 041__ $$aeng
000168469 100__ $$0(orcid)0000-0001-5603-3045$$aBarrio, E$$uUniversidad de Zaragoza
000168469 245__ $$aFamilial short stature and intrauterine growth retardation associated with a novel mutation in the IGF-I (IGF1R) receptor gene
000168469 260__ $$c2013
000168469 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168469 5203_ $$aSummary: Context IGF-I is essential for normal human growth and mediates its effects through the IGF1R. IGF1R mutations have been associated with varying degrees of intrauterine and postnatal growth retardation. Objective To identify IGF1R gene mutations in a short-statured family with intrauterine growth retardation and microcephaly. Methods Direct DNA sequencing was used to identify IGF1R mutations. Multiplex ligation-dependent probe amplification analyses were performed for deletions and duplications of all IGF1R exons. Functional studies were conducted to assess mutation pathogenicity. Results A novel heterozygous IGF1R missense mutation in exon 7 (c.A1549T, p.Y487F) was identified in a short-statured girl with severe prenatal growth retardation and microcephaly. The same mutation was also identified in her mother, who presented
prenatal and postnatal growth failure, and her short-statured maternal grandmother, both of whom exhibited microcephaly. The index case showed a partial response to rhGH. Functional studies performed in dermal fibroblasts from the index case and her mother showed normal IGF-I binding; however, IGF-I activation of intracellular signalling measured as AKT and extracellular signal–regulated kinase phosphorylation was markedly reduced, with patients’ values being lower than those of her mother. IGF-I stimulation of DNA synthesis was significantly reduced compared with controls. Conclusion Our results show a novel missense mutation in the IGF1R gene (c.A1549T, p.Y487F) associated with prenatal and postnatal growth failure and microcephaly in the context of familial short stature. The functional studies are in line with the inactivation of one copy of the IGF1R gene with variable expression within the same family.
000168469 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI07-0145
000168469 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000168469 590__ $$a3.353$$b2013
000168469 591__ $$aENDOCRINOLOGY & METABOLISM$$b53 / 121 = 0.438$$c2013$$dQ2$$eT2
000168469 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000168469 700__ $$0(orcid)0000-0003-2832-2266$$aLabarta-Aizpún, JI.$$uUniversidad de Zaragoza
000168469 700__ $$aAudi, L
000168469 700__ $$aFernández-Cancio, M
000168469 700__ $$aAndaluz, P
000168469 700__ $$0(orcid)0000-0002-2865-5813$$aDe Arriba, A
000168469 700__ $$aPuga, B
000168469 700__ $$aCalvo, MT
000168469 700__ $$aMayayo, E
000168469 700__ $$aCarrascosa, A
000168469 700__ $$aFerrández-Longás, A
000168469 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000168469 7102_ $$11010$$2670$$aUniversidad de Zaragoza$$bDpto. Pediatría Radiol.Med.Fís$$cÁrea Pediatría
000168469 773__ $$g78, 2 (2013), 255-262$$pClin. endocrinol.$$tCLINICAL ENDOCRINOLOGY$$x0300-0664
000168469 8564_ $$s592093$$uhttps://zaguan.unizar.es/record/168469/files/texto_completo.pdf$$yPostprint
000168469 8564_ $$s1071782$$uhttps://zaguan.unizar.es/record/168469/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000168469 909CO $$ooai:zaguan.unizar.es:168469$$particulos$$pdriver
000168469 951__ $$a2026-02-10-08:48:30
000168469 980__ $$aARTICLE