Partial Primary Deficiency of Insulin-Like Growth Factor (IGF)-I Activity Associated with<i>IGF1</i>Mutation Demonstrates Its Critical Role in Growth and Brain Development

Netchine, Irène; Azzi, Salah; Houang, Muriel; Seurin, Danielle; Périn, Laurence; Ricort, Jean‐Marc; Daubas, Claudine; Legay, Christine; Mešter, Ján; Herich, R.; Godeau, François; Bouc, Yves Le

doi:10.1210/jc.2009-0452

Cited by 123 publications

(62 citation statements)

References 33 publications

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“…Patients with a homozygous hypomorphic mutation (72) or specific heterozygous mutations (73,74) presented with less severe growth failure and normal hearing (reviewed in (75)). Heterozygous carriers of IGF1 mutations or deletions are w1 S.D.…”

Section: Gh Deficiencymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

141

132

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The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T 3 /T 4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in w3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders.

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Section: Gh Deficiencymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

141

132

View full text Add to dashboard Cite

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“…The severity of the foetal growth restriction is illustrated with birth weight standard deviation scores (SDS) ranging from −2.5 to −3.5 (Table 1) 36, 37, 38, 39, 40.…”

Section: Organ‐specific Roles Of Igf‐1 In the Foetusmentioning

confidence: 99%

“…All the reported IGF‐1 gene defects in viable humans have been associated with microcephaly and developmental delay (36, 40,S64–66) (Table 1). There is improved general growth with IGF‐1 treatment, including brain growth, which is reflected in increased head circumferences in children with growth hormone insensitivity syndrome (S67,S68).…”

Section: Organ‐specific Roles Of Igf‐1 In the Foetusmentioning

confidence: 99%

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

et al. 2016

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Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin‐like growth factor 1 (IGF‐1) axis is the major hormonal mediator of growth in utero, and levels of IGF‐1 are often very low after preterm birth. We reviewed the role of IGF‐1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF‐1 deficiency in preterm morbidities.ConclusionThere is a rationale for clinical trials to evaluate the potential benefits of IGF‐1 replacement in very preterm infants.

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“…Severe IGF1 deficiency due to a homozygous mutation in the IGF1 gene results in intrauterine and postnatal growth failure, microcephaly, intellectual disability, and deafness (3,4,5,6). Mutations in the IGF1R gene in the heterozygous state have been recently described as a cause of IUGR (7) and lead to partial resistance to IGF1 and contribute to IUGR with postnatal growth failure, microcephaly, and normal or increased levels of serum IGF1 and IGF binding protein 3 (IGFBP3), sometimes associated with modestly impaired intellectual development (8,9,10,11,12,13,14,15,16,17,18,19,20,21).…”

Section: Introductionmentioning

confidence: 99%

Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations

Gannagé‐Yared

Klammt²,

Chouery

et al. 2013

European Journal of Endocrinology

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Background: Heterozygous mutations in the IGF1 receptor (IGF1R) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure. To date, homozygous mutations of this receptor have not been described. Subject: A 13.5-year-old girl born from healthy first-cousin parents presented with severe IUGR and persistent short stature. Mild intellectual impairment, dysmorphic features, acanthosis nigricans, and cardiac malformations were also present. Methods: Auxological and endocrinological profiles were measured. All coding regions of the IGF1R gene including intron boundaries were amplified and directly sequenced. Functional characterization was performed by immunoblotting using patient's fibroblasts. Results: IGF1 level was elevated at 950 ng/ml (C7 S.D.). Fasting glucose level was normal associated with high insulin levels at baseline and during an oral glucose tolerance test. Fasting triglyceride levels were elevated. Sequencing of the IGF1R gene led to the identification of a homozygous variation in exon 2: c.119GOT (p.Arg10Leu). As a consequence, IGF1-dependent receptor autophosphorylation and downstream signaling were reduced in patient's fibroblasts. Both parents were heterozygous for the mutation. Conclusion: The homozygous mutation of the IGF1R is associated with severe IUGR, dysmorphic features, and insulin resistance, while both parents were asymptomatic heterozygous carriers of the same mutation.

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Partial Primary Deficiency of Insulin-Like Growth Factor (IGF)-I Activity Associated withIGF1Mutation Demonstrates Its Critical Role in Growth and Brain Development

Cited by 123 publications

References 33 publications

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations

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