Genetic disorders in the GH–IGF-I axis in mouse and man

Abstract

Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH-IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH-IGF-I axis in order to describe the role of the GH-IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH-IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH-IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH-IGF-I axis for the patient and the therapeutic options will be discussed.European Journal of Endocrinology 157 S15-S26

Homozygous and heterozygous expression of a novel mutation of the acid-labile subunit

“…been presented in earlier reports; thus it remains to be established whether microcephaly represents a clinical feature of homozygous ALS deficiency. The growth pattern in humans with ALS deficiency is comparable with the mild growth failure observed in ALS gene knock-out (ALS-KO) mice, and is in contrast with the severe growth failure as observed in patients with a total IGF-I deficiency (2). This is in line with the hypothesis that the contribution of locally produced IGF-I to longitudinal growth is more important than that of IGF-I derived from the circulation (10,17).…”

“…Puberty onset was reported to have occurred between 12 and 14 years. Total BMD at 6, 10, and 12 years of age was 0.68 (K1.3 SDS), 0.76 (K1.2 SDS), and 0.62 g/cm 2 (K2.0 SDS) respectively. The GH peak after exercise was high (118 mU/l), IGF-I was very low (K4.2 to K3.8 SDS), and IGFBP-3 extremely low (!K17 SDS).…”

“…For both humans and rodents, it has been well established that insulin-like growth factor-I (IGF-I) plays a critical role in the regulation of intrauterine growth and development and postnatal growth and metabolism (1,2). Total IGF-I deficiency leads to severe intrauterine and postnatal growth failure, microcephaly, mental retardation, and deafness (3,4).…”

Acromegaly Accompanied by Turner Syndrome with 47,XXX/45,X/46,XX Mosaicism

“…However, our patient seems to have secreted estrogen sufficiently because she had her periods before the tumor developed. Therefore GH secretion may have been promoted probably because of increased GHRH secretion if she was in a state of GH/IGF-I insensitivity (26,27). A previous study showed that excessive GH secretion resulted in upregulated somatotrope proliferation and neoplastic transformation in animal models and human (28).…”

Dairy intake associates with the IGF rs680 polymorphism to height variation in periadolescent children

“…The insulin-like growth factors (IGFs) are powerful mitogenic agents that stimulate cell differentiation and inhibit apoptosis (Walenkamp and Wit, 2007). IGF2, located on chromosome 11p15.5, also known as somatomedin A, is a single-chain polypeptide that shares an amino acid sequence homology of about 47% with insulin and 31% with relaxin.…”