Familial short stature with IGF-I receptor gene anomaly [Review]

Kawashima, Yuki; Takahashi, Shin‐Ichiro; Kanzaki, Sho

doi:10.1507/endocrj.ej11-0258

Cited by 19 publications

(17 citation statements)

References 35 publications

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“…These patients are phenotypically distinct from the patients with the IGF-1 gene mutation described by Woods et al [36]. IGF-1R gene variants, including heterozygous IGF-1R mutations or haploinsufficiency of this gene, should be investigated in subjects with FSS [38]. …”

Section: Etiology and Classificationmentioning

confidence: 99%

Challenges in the Management of Short Stature

Argente¹

2015

Horm Res Paediatr

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Human growth, from fetal life to adolescence, is dynamic and a good marker of health. Growth is a complex process influenced by genetic, hormonal, nutritional and environmental factors, both pre- and postnatally. To date, no international agreement regarding normal height has been established. Auxological parameters are fundamental to investigate potential short stature (SS), either with a known diagnosis, e.g. disproportionate or proportionate, prenatal and/or postnatal onset, or an unknown diagnosis, i.e. idiopathic SS. The incidence/prevalence of SS is difficult to establish. The measurement of choice in children aged <2 years is length, while in those >2 years of age it is height. A number of monogenic diseases that lead to proportionate SS due to either isolated growth hormone deficiency, multiple pituitary hormone deficiency, growth hormone insensitivity, primary acid-labile subunit deficiency, primary IGF-1 deficiency, IGF-1 resistance, primary IGF-2 deficiency or primary protease deficiency have been discovered in the last 30 years. In addition, the Nosology and Classification of Genetic Skeletal Disorders revised in 2015 includes 436 conditions, with a number of genes of 364. A practical algorithm for the evaluation of SS as well as therapeutic options are discussed.

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Section: Etiology and Classificationmentioning

confidence: 99%

Challenges in the Management of Short Stature

Argente¹

2015

Horm Res Paediatr

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“…Mice with a homozygous deletion of the gene encoding the IGF-I high affinity receptor ( Igf1r ) show a delayed ossification in the cranial and facial bones, inner ear alterations and die shortly after birth [10], [11]. Furthermore, partial deletion of the Igf1r gene causes postnatal growth retardation in humans [12]. IGF1R activation recruits insulin receptor substrates (IRS).…”

Section: Introductionmentioning

confidence: 99%

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

et al. 2014

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Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-κB ligand ratio, Wnt3a , cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone.

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“…The first human IGF-1R mutation was discovered during the screening of SGA in Germany and the US in 2003. Many clinical studies have shown that IGF-1R gene mutations were related to short stature (Yu, 2011;Kawashima et al, 2012), such as SGA and intrauterine growth retardation (Klammt et al, 2008). Phenomena such as insensitivity to GH and IGF-1 resistance have been found in ISS patients (Cohen et al, 2010), which suggested that ISS might be related to IGF-1R gene abnormalities.…”

Section: Discussionmentioning

confidence: 99%