The Syndrome of Pituitary Dwarfism With High Serum Concentration of Growth Hormone

Laron, Zvi; Pertzelan, A

doi:10.1530/acta.0.056s018

Cited by 189 publications

(244 citation statements)

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“…Deficiency in GHR signaling, due to gene mutations in humans, results in various degrees of dwarfism, with the most extreme cases resulting in Laron-type dwarfism (Laron et al 1966;Amselem et al 1989;Kelly et al 1991;Laron and Klinger 1994). These disorders are controlled by defective alleles at major loci referring to hormones or hormone receptors.…”

Section: Discussionmentioning

confidence: 99%

“…The BNMP has served as an ideal experimental model of human disease in the biomedical field due to its anatomical, physiological and metabolic similarities to human beings. Most recent studies on the mechanisms causing dwarfism have focused on the human Laron syndrome and on sexlinked dwarfism in chickens (Laron et al 1966;Amselem et al 1989;Burnside et al 1991Burnside et al , 1992Kelly et al 1991;Huang et al 1993;Laron and Klinger 1994). However, the growth-regulating mechanism of dwarfism in miniature pigs remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Growth hormone and receptor gene mutations in Chinese Banna miniature pig

Deng

Hao

et al. 2011

Animal Cells and Systems

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The Banna miniature pig (BNMP) is a representative miniature pig breed in China. Even though BNMP dwarfism is obvious, its underlying causative mutations remain unknown. In this study, the BNMP and Large White pig (LWP) serum growth hormone (GH) and insulin-like growth factor (IGF-1) levels were detected by ELISA and compared. BNMP serum IGF-1 levels were significantly lower than LWP levels (P B0.05). The miniature condition may arise from mutations in the GH and GH receptor (GHR) genes. Therefore, GH and GHR cDNA from the BNMP were cloned into a pMD18-T vector by RT-PCR using the total RNA obtained from the BNMP's pituitary and liver tissues. Sequencing results indicated that the open reading frame of the BNMP GH gene is composed of a 26-residue signal peptide and a 191-residue mature peptide. The coding sequence of the BNMP GHR gene contained 639 amino acids, including a signal peptide that is 18 amino acids long. Two amino acid substitutions, A09V and R22Q, were found in the signal peptide of the GH gene. Additionally, the S104P mutation was found in the BNMP's mature GH protein. Four mutations in the cytoplasmic domain of GHR may influence the downstream signal transduction of GHR, which needs further experimental evidence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Growth hormone and receptor gene mutations in Chinese Banna miniature pig

Deng

Hao

et al. 2011

Animal Cells and Systems

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“…The classic phenotype of severe growth failure associated with elevated serum GH concentrations was first described by Laron et al [16] and can be classified as primary IGF-1 deficiency [17,18]. Severe forms of primary IGF-1 deficiency have been observed with molecular defects involving the GH receptor (GHR), the GHR cascade and IGF-1/acid-labile subunit/IGFBP-3 ternary complex as well as the type 1 IGF receptor.…”

Section: Gh Insensitivity (Ghi)mentioning

confidence: 99%

Biological Determinants of Responsiveness to Growth Hormone: Pharmacogenomics and Personalized Medicine

Mullis¹

2010

Current Indications for Growth Hormone Therapy

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It is becoming most clear that many genes are involved in controlling the regulation of growth. Ultimately however, at the level of growth hormone (GH), the relevant question may be not whether a patient is GH-deficient, but whether he is GH-responsive. As these disturbances can be divided into two gross categories, namely alterations causing subnormal GH secretion and/or those presenting with subnormal GH sensitivity/responsiveness, the main aim of this review is to focus on genes involved in growth regulation leading to short stature caused by an alteration of GH insensitivity/GH responsiveness; in other words, clinical circumstances where individually adapted GH replacement therapy may help to increase height velocity and eventually final height.

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“…Laron syndrome (Laron et al, 1966), a rare autosomal recessive disorder, is characterized by a severely short stature resistant to growth hormone (GH). The cause of the syndrome, a partial deletion and a mutation of the growth hormone receptor (GHR) gene (GHR), were identified in 1989 (Godowski et al, t989;Amselem et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…The cause of the syndrome, a partial deletion and a mutation of the growth hormone receptor (GHR) gene (GHR), were identified in 1989 (Godowski et al, t989;Amselem et al, 1989). Although the short stature in Laron syndrome patients is clinically indistinguishable from that in isolated GH-deficient patients (Laron et al, 1966), other manifestations such as a low level of insulin-like growth factor-I (IGF-I) despite a high GH level, a lack of GH binding in the liver microsomal membrane (Eshet et aL, 1984), a tow level or absence of serum GH-binding protein (GHBP) (Daughaday and Trivedi, 1987;Baumann et aL, 1987;Laron et al, 1989), and no response to exogenous GH characterize this syndrome.…”

Section: Introductionmentioning

confidence: 99%

The growth hormone receptor gene mutation of a japanese patient with laron syndrome

et al. 1997

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SummaryDeletions and point mutations of the growth hormone (GH) receptor gene (GHR) have been identified in patients with Laron syndrome. We report the first detection of the GHR mutation among Japanese patients with Laron syndrome. Using the Japanese female patient's genomic DNA as a template, all exons and flanking portions of introns of GHR were amplified by polymerase chain reaction (PCR). Sequencing of the PCR products showed that the patient was homozygous for a G to A substitution at the first position of intron 4. This substitution was same as that detected in a Spanish patient and a north European patient. The base change occurred at the 5' splice consensus sequence of intron 4, resulting in the abolition of a BanI restriction site. Since this substitution was not detected by a BanI restriction analysis in 85 control individuals, it is more likely a disease-related splice mutation than a polymorphism. The mutation in our patient was predicted to destroy the original 5" splice site of intron 4 of GHR and to produce a new cryptic splice site, leading to abnormal mRNA processing and a lack of GH binding activity of GH-binding protein (GHBP).

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The Syndrome of Pituitary Dwarfism With High Serum Concentration of Growth Hormone

Cited by 189 publications

References 0 publications

Growth hormone and receptor gene mutations in Chinese Banna miniature pig

Growth hormone and receptor gene mutations in Chinese Banna miniature pig

Biological Determinants of Responsiveness to Growth Hormone: Pharmacogenomics and Personalized Medicine

The growth hormone receptor gene mutation of a japanese patient with laron syndrome

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