Genomes and Genes
Gene Symbol: IGF-1
Description: insulin like growth factor 1
Alias: IGF-I, IGFI, MGF, insulin-like growth factor I, insulin-like growth factor 1 (somatomedin C), insulin-like growth factor IB, mechano growth factor, somatomedin-C
- Johansson P, Aberg D, Johansson J, Mattsson N, Hansson O, Ahren B, et al. Serum but not cerebrospinal fluid levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) are increased in Alzheimer's disease. Psychoneuroendocrinology. 2013;38:1729-37 pubmed publisher..42, P=0.02). Patients with AD as well as other dementias had high levels of IGF-I in serum but not in CSF. In AD patients, the IGF-I system was associated with biomarkers of AD disease status. ..
- Dong X, Chang G, Ji X, Tao D, Wang Y. The relationship between serum insulin-like growth factor I levels and ischemic stroke risk. PLoS ONE. 2014;9:e94845 pubmed publisher..Thus, strokes were more likely to occur in patients with low serum IGF-I levels in the Chinese population; further, post-ischemic IGF-I therapy may be beneficial for stroke. ..
- Jiang B, Zhang X, Du L, Wang Y, Liu D, Han C, et al. Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer. World J Gastroenterol. 2014;20:1608-13 pubmed publisher..The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease. ..
- Li Z, Ying X, Chen H, Ye P, Chen Z, Li G, et al. Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer. World J Gastroenterol. 2013;19:7788-94 pubmed publisher..To investigate the expression of insulin-like growth factor-1 (IGF-1)/insulin-like growth factor-1 receptor (IGF-1R) in colorectal cancer (CRC) tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis...
- Castro G, Coelho J, Parolin M, Matias J, de Freitas A. Insulin-like growth factor I correlates with MELD and returns to normal level after liver transplantation. Ann Transplant. 2013;18:57-62 pubmed publisher..7±82.8 and 4.14±1.1 ng/mL, respectively) (p<0.001). Low levels of IGF-I and IGFBP-3 observed in patients with advanced liver cirrhosis are corrected after OLT. IGF-I and IGFBP-3 correlate negatively with MELD. ..
- Lau M, Leung P. The PI3K/Akt/mTOR signaling pathway mediates insulin-like growth factor 1-induced E-cadherin down-regulation and cell proliferation in ovarian cancer cells. Cancer Lett. 2012;326:191-8 pubmed publisher..This study demonstrates a novel mechanism in which IGF1 down-regulates E-cadherin expression through the activation of PI3K/Akt/mTOR signaling and the up-regulation of Snail and Slug in human ovarian cancer cells. ..
- Duggan C, Wang C, Neuhouser M, Xiao L, Smith A, Reding K, et al. Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer. Int J Cancer. 2013;132:1191-200 pubmed publisher..In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts. ..
- Fletcher O, Gibson L, Johnson N, Altmann D, Holly J, Ashworth A, et al. Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:2-19 pubmed..Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely. ..
- Hernandez W, Grenade C, Santos E, Bonilla C, Ahaghotu C, Kittles R. IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans. Carcinogenesis. 2007;28:2154-9 pubmed..Our study adds clarity and further support to the previous findings, implicating serum IGFBP-3 levels and the IGFBP-3 -202 A/C SNP in prostate carcinogenesis. ..
- Jernstrom H, Chu W, Vesprini D, Tao Y, Majeed N, Deal C, et al. Genetic factors related to racial variation in plasma levels of insulin-like growth factor-1: implications for premenopausal breast cancer risk. Mol Genet Metab. 2001;72:144-54 pubmed..The high incidence of premenopausal breast cancer among black women may be mediated through genetic modifiers of circulating levels of IGF-I. ..
- Tazearslan C, Huang J, Barzilai N, Suh Y. Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles. Aging Cell. 2011;10:551-4 pubmed publisher..These results demonstrate that the human longevity-associated IGF1R variants are reduced-function mutations, implying that dampening of IGF1 signaling may be a longevity mechanism in humans. ..
- Lam C, Chen M, Lacey S, Yang Q, Sullivan L, Xanthakis V, et al. Circulating insulin-like growth factor-1 and its binding protein-3: metabolic and genetic correlates in the community. Arterioscler Thromb Vasc Biol. 2010;30:1479-84 pubmed publisher..Prospective studies are warranted to elucidate whether lower IGF-1 concentrations predict greater metabolic risk longitudinally. ..
- Feik E, Baierl A, Hieger B, Führlinger G, Pentz A, Stättner S, et al. Association of IGF1 and IGFBP3 polymorphisms with colorectal polyps and colorectal cancer risk. Cancer Causes Control. 2010;21:91-7 pubmed publisher..39, 95% CI 1.01-1.90). Our results suggest that the SNP rs6214 of IGF1 could have an impact on developing colorectal cancer and colorectal polyps with villous elements. ..
- Burchardt P, Nowak W, Gozdzicka Jozefiak A, Link R, Grotowski T, Wisniecka A, et al. Presence of irregularity in region between -1115 and -784 nt in P1 promoter of insulin-like growth factor-1 gene may indicate beneficial effect on coronary arteries in a group of patients with stable angina: preliminary data. Heart Vessels. 2009;24:254-9 pubmed publisher..We presume that presence of SSCP in the P1 region between -1115 and -784 nt may positively affect coronary arteries by increasing circulating IGF-1 levels, but its clinical importance requires molecular verification and further studies. ..
- D Aloisio A, Schroeder J, North K, Poole C, West S, Travlos G, et al. IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women. Cancer Epidemiol Biomarkers Prev. 2009;18:954-66 pubmed publisher..Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels. ..
- Diorio C, Brisson J, Bérubé S, Pollak M. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev. 2008;17:880-8 pubmed publisher....
- Geelhoed J, Mook Kanamori D, Witteman J, Hofman A, van Duijn C, Moll H, et al. Variation in the IGF1 gene and growth in foetal life and infancy. The Generation R Study. Clin Endocrinol (Oxf). 2008;68:382-9 pubmed..Studies in larger cohorts are necessary to replicate our findings and to examine whether these effects persist throughout childhood. ..
- González Zuloeta Ladd A, Liu F, Houben M, Arias Vasquez A, Siemes C, Janssens A, et al. IGF-1 CA repeat variant and breast cancer risk in postmenopausal women. Eur J Cancer. 2007;43:1718-22 pubmed..26 (95% CI=0.95-1.82) for IGF-I CA(19) non-carriers versus CA(19) homozygous carriers. According to these results, the IGF-I CA(19) promoter polymorphism is not likely to predict the risk of breast cancer. ..
- Twigg S, Baxter R. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 1998;273:6074-9 pubmed..The demonstration of IGFBP-5-containing ternary complexes indicates an unrecognized form of IGF transport in the circulation and an additional mechanism for regulating IGF bioavailability. ..
- Ueki I, Ooi G, Tremblay M, Hurst K, Bach L, Boisclair Y. Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system. Proc Natl Acad Sci U S A. 2000;97:6868-73 pubmed..This model should be useful to determine whether presence of ALS is needed for other actions of liver-derived IGF-I and for maintenance of homeostasis in presence of high circulating levels of IGF-II. ..
- Delafontaine P, Song Y, Li Y. Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler Thromb Vasc Biol. 2004;24:435-44 pubmed..This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases. ..
- Musaro A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, et al. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet. 2001;27:195-200 pubmed..The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty. ..
- Vaessen N, Heutink P, Janssen J, Witteman J, Testers L, Hofman A, et al. A polymorphism in the gene for IGF-I: functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes. 2001;50:637-42 pubmed..4 (95% CI 1.1-11.3). Our study suggests that a genetically determined exposure to relatively low IGF-I levels is associated with an increased risk for type 2 diabetes and myocardial infarction. ..
- Jernstrom H, Deal C, Wilkin F, Chu W, Tao Y, Majeed N, et al. Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev. 2001;10:377-84 pubmed..Our results support the view that circulating IGF-I levels and IGFBP-3 levels are complex traits and are influenced by a number of interacting genetic and nongenetic factors. ..
- Boucher J, Tseng Y, Kahn C. Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. J Biol Chem. 2010;285:17235-45 pubmed publisher..Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. ..
- Yang T, Xiong D, Guo Y, Recker R, Deng H. Comprehensive association analyses of IGF1, ESR2, and CYP17 genes with adult height in Caucasians. Eur J Hum Genet. 2008;16:1380-7 pubmed publisher..It will be valuable for other independent studies to replicate and confirm these findings. ..
- Sadowski T, Dietrich S, Koschinsky F, Sedlacek R. Matrix metalloproteinase 19 regulates insulin-like growth factor-mediated proliferation, migration, and adhesion in human keratinocytes through proteolysis of insulin-like growth factor binding protein-3. Mol Biol Cell. 2003;14:4569-80 pubmed..This activity might have widespread consequences for the behavior of epidermal keratinocytes. ..
- Brokaw J, Katsaros D, Wiley A, Lu L, Su D, Sochirca O, et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors. 2007;25:346-54 pubmed publisher..The study also suggests that both endocrine and paracrine/autocrine are involved in the regulation of IGF-I activity in ovarian cancer. ..
- Hilmi C, Larribere L, Giuliano S, Bille K, Ortonne J, Ballotti R, et al. IGF1 promotes resistance to apoptosis in melanoma cells through an increased expression of BCL2, BCL-X(L), and survivin. J Invest Dermatol. 2008;128:1499-505 pubmed..These findings therefore delineate the molecular mechanisms by which IGF1 mediates its prosurvival properties and provide a basis for clinical strategies designed to neutralize IGF1 or its target genes. ..
- McGrath M, Lee I, Buring J, De Vivo I. Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk. Gynecol Oncol. 2011;120:174-8 pubmed publisher..NHS) and the Women's Health Study (WHS) to investigate the association between forty-four polymorphisms within IGFI, IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive endometrial cancer cases and 1723 ..
- Kaplan R, Petersen A, Chen M, Teumer A, Glazer N, Doring A, et al. A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3. Hum Mol Genet. 2011;20:1241-51 pubmed publisher..These genetic loci deserve further investigation to elucidate the biological basis for the observed associations and clarify their possible role in IGF-mediated regulation of cell growth and metabolism. ..
- Rivadeneira F, Houwing Duistermaat J, Beck T, Janssen J, Hofman A, Pols H, et al. The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam Study. J Bone Miner Res. 2004;19:1280-90 pubmed..The CA-repeat promoter polymorphism in the IGF-I gene is associated with the risk for fragility fracture at old age in women and with bone structure in both genders. ..
- Johnston L, Dahlgren J, Leger J, Gelander L, Savage M, Czernichow P, et al. Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations. J Clin Endocrinol Metab. 2003;88:4805-10 pubmed..These studies validate the association of the IGF-I gene with birth size and refine the region of association in Swedish short SGA subjects. ..
- Aberg D, Jood K, Blomstrand C, Jern C, Nilsson M, Isgaard J, et al. Serum IGF-I levels correlate to improvement of functional outcome after ischemic stroke. J Clin Endocrinol Metab. 2011;96:E1055-64 pubmed publisher..001; r = 0.174, and P < 0.001; r = 0.24, respectively). A high s-IGF-I during the rehabilitation phase of stroke correlates to better recovery of long-term function. ..
- Zhao J, Xiong D, Guo Y, Yang T, Recker R, Deng H. Polymorphism in the insulin-like growth factor 1 gene is associated with age at menarche in caucasian females. Hum Reprod. 2007;22:1789-94 pubmed..Our results suggested a potential effect of SNP3 in the IGF1 gene on AAM variation in Caucasian women for the first time. However, further independent studies are needed to confirm our findings. ..
- Tamimi R, Cox D, Kraft P, Pollak M, Haiman C, Cheng I, et al. Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study. Breast Cancer Res. 2007;9:R18 pubmed..2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005). Common genetic variation in IGF1 is strongly associated with percentage mammographic density. ..
- Camacho Hubner C, Woods K, Clark A, Savage M. Insulin-like growth factor (IGF)-I gene deletion. Rev Endocr Metab Disord. 2002;3:357-61 pubmed
- Missmer S, Haiman C, Hunter D, Willett W, Colditz G, Speizer F, et al. A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer. Int J Cancer. 2002;100:332-6 pubmed..Although a modest association cannot be excluded, our data do not support an important relation between this IGF-1 gene polymorphism and breast cancer risk. ..
- Shen M, Hsu Y, Hsu K, Chen Y, Tang M, Chou C. Insulin-like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by alphavbeta3 integrin signaling. Carcinogenesis. 2006;27:962-71 pubmed..Thus, these data suggest that the signal interaction between IGF-1R and alpha(v)beta3 integrin plays an important role in promoting the development and progression of cervical cancer. ..
- Al Zahrani A, Sandhu M, Luben R, Thompson D, Baynes C, Pooley K, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet. 2006;15:1-10 pubmed..More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective. ..
- Fowke J, Matthews C, Yu H, Cai Q, Cohen S, Buchowski M, et al. Racial differences in the association between body mass index and serum IGF1, IGF2, and IGFBP3. Endocr Relat Cancer. 2010;17:51-60 pubmed publisher..The effects of obesity throughout life on the IGF axis and racial differences in breast cancer risk require study. ..
- Rozing M, Westendorp R, Frolich M, de Craen A, Beekman M, Heijmans B, et al. Human insulin/IGF-1 and familial longevity at middle age. Aging (Albany NY). 2009;1:714-22 pubmed....
- DeLellis K, Ingles S, Kolonel L, McKean Cowdin R, Henderson B, Stanczyk F, et al. IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort. Br J Cancer. 2003;88:277-82 pubmed..Research into relevant determinants of IGF1 levels in the blood must continue. ..
- Qian B, Zheng H, Yu H, Chen K. Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women. Breast Cancer Res Treat. 2011;130:217-26 pubmed publisher....
- Wen W, Gao Y, Shu X, Yu H, Cai Q, Smith J, et al. Insulin-like growth factor-I gene polymorphism and breast cancer risk in Chinese women. Int J Cancer. 2005;113:307-11 pubmed..22, 95% CI: 1.06-1.41, p for heterogeneity test = 0.524). The findings of this study support the hypothesis that IGF-I gene polymorphisms may be a significant genetic factor for breast cancer susceptibility. ..
- Chen W, Wang S, Tian T, Bai J, Hu Z, Xu Y, et al. Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet. 2009;17:1668-75 pubmed publisher..001). In conclusion, circulating levels of IGF1, IGFBP3 and IGFBP3 A-202C play a crucial role in carcinogenesis and could serve as susceptibility biomarkers for cancer development. ..
- Bonapace G, Concolino D, Formicola S, Strisciuglio P. A novel mutation in a patient with insulin-like growth factor 1 (IGF1) deficiency. J Med Genet. 2003;40:913-7 pubmed
- Kaplan Lefko P, Sutherland B, Evangelou A, Hadsell D, Barrios R, Foster B, et al. Enforced epithelial expression of IGF-1 causes hyperplastic prostate growth while negative selection is requisite for spontaneous metastogenesis. Oncogene. 2008;27:2868-76 pubmed..Selection against IGF-1 action appears requisite for progression of localized disease and metastogenesis. ..
- Guernec A, Chevalier B, Duclos M. Nutrient supply enhances both IGF-I and MSTN mRNA levels in chicken skeletal muscle. Domest Anim Endocrinol. 2004;26:143-54 pubmed....
- Gonzalez E, Messi M, Zheng Z, Delbono O. Insulin-like growth factor-1 prevents age-related decrease in specific force and intracellular Ca2+ in single intact muscle fibres from transgenic mice. J Physiol. 2003;552:833-44 pubmed..Therefore, IGF-1 prevents age-related decline in peak intracellular Ca2+ and specific force in a muscle that does not exhibit changes in fibre type composition with senescence. ..
- Deming S, Ren Z, Wen W, Shu X, Cai Q, Gao Y, et al. Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study. Breast Cancer Res Treat. 2007;104:309-19 pubmed..Taken together, these data suggest that polymorphisms in the IGF-1R and IGFBP3 genes may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status. ..
- Landmann E, Geller F, Schilling J, Rudloff S, Foeller Gaudier E, Gortner L. Absence of the wild-type allele (192 base pairs) of a polymorphism in the promoter region of the IGF-I gene but not a polymorphism in the insulin gene variable number of tandem repeat locus is associated with accelerated weight gain in infancy. Pediatrics. 2006;118:2374-9 pubmed..The IGF-I 192-base pair allele may reduce the risk for rapid weight gain in early infancy. ..
- Joung Y, Lee M, Lim E, Kim M, Hwang T, Kim S, et al. Hypoxia activates the IGF-1 expression through STAT5b in human HepG2 cells. Biochem Biophys Res Commun. 2007;358:733-8 pubmed..STAT5b expression was inhibited by siRNA experiments leading to decreased IGF-1. These results provide a basis of molecular targets for cancer treatment via the STAT5b-IGF-1 pathway in solid tumor cells. ..
- Woods K, Camacho Hubner C, Savage M, Clark A. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med. 1996;335:1363-7 pubmed
- Canzian F, McKay J, Cleveland R, Dossus L, Biessy C, Rinaldi S, et al. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study. Br J Cancer. 2006;94:299-307 pubmed..Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians. ..
- Voorhoeve P, van Rossum E, te Velde S, Koper J, Kemper H, Lamberts S, et al. Association between an IGF-I gene polymorphism and body fatness: differences between generations. Eur J Endocrinol. 2006;154:379-88 pubmed....
- Wagner K, Hemminki K, Forsti A. The GH1/IGF-1 axis polymorphisms and their impact on breast cancer development. Breast Cancer Res Treat. 2007;104:233-48 pubmed..We point out what is known about the effects of the variants and show how the interaction of genetic variants affects breast cancer risk. ..
- Kaplan R, Buzkova P, Cappola A, Strickler H, McGinn A, Mercer L, et al. Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97:1970-6 pubmed publisher..Among older adults, decreasing IGF-I level over time does not predict subsequent all-cause mortality, whereas increasing IGFBP-1 predicts increased risk of mortality. ..
- Rietveld I, Janssen J, van Rossum E, Houwing Duistermaat J, Rivadeneira F, Hofman A, et al. A polymorphic CA repeat in the IGF-I gene is associated with gender-specific differences in body height, but has no effect on the secular trend in body height. Clin Endocrinol (Oxf). 2004;61:195-203 pubmed..The secular trend in body height observed in our elderly Dutch population was similar for the different genotypes; carriers of the 192-bp and/or the 194-bp allele remained significantly taller throughout time. ..
- Weiss J, Huang W, Rinaldi S, Fears T, Chatterjee N, Chia D, et al. IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Int J Cancer. 2007;121:2267-73 pubmed..11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men. ..
- Ma J, Sawai H, Matsuo Y, Ochi N, Yasuda A, Takahashi H, et al. IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells. J Surg Res. 2010;160:90-101 pubmed publisher..We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-small ka, CyrillicB might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer. ..
- Netchine I, Azzi S, Houang M, Seurin D, Perin L, Ricort J, et al. Partial primary deficiency of insulin-like growth factor (IGF)-I activity associated with IGF1 mutation demonstrates its critical role in growth and brain development. J Clin Endocrinol Metab. 2009;94:3913-21 pubmed publisher..The characterization of this complex phenotype and identification of such molecular defects have therapeutic implications, particularly now that, in addition to GH, recombinant IGF-I is available for clinical use. ..