A case report and literature review of monoallelic mutation of GHR

Mitani, Marie; Shima, Hirohito; Satô, Takeshi; Inoguchi, Tomohiro; Kamimaki, Tsutomu; Fukami, Maki; Hasegawa, Tomonobu

doi:10.1515/jpem-2018-0365

Cited by 2 publications

(2 citation statements)

References 8 publications

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“…Biallelic variants in the GHR are the most prevalent causes for primary GHI syndrome with classical GHI, phenotypically presenting with severe short stature and prominent insulin-like growth factor (IGF)-1 deficiency. Recently, milder GHI syndrome has been reported to be caused by rare monoallelic GHR mutations that can lead to a dominant-negative effect [ 49 , 59 , 69 ].…”

Section: Introductionmentioning

confidence: 99%

“…Today around 100 variants have been identified in the GHR gene that can cause dwarfism in humans, including missense, deletion, nonsense, frameshift and splice site variants. These variants affect signal transduction, ligand binding, and GHR dimerization [ 44 , 49 ]. Studies have shown that recombinant IGF-1 therapy is the only effective treatment and can improve height z-score in LS cases compared to untreated patients, although standard height may not be achieved.…”

Section: Introductionmentioning

confidence: 99%

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Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report

Bitarafan,

Khodaeian,

Garrousi

et al. 2023

BMC Endocr Disord

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Background Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth factor (IGF)-1. Pathogenic variants in the GHR gene can result in structural and functional defects in the GHR protein, leading to Laron Syndrome (LS) with the primary clinical manifestation of short stature. So far, around 100 GHR variants have been reported, mostly biallelic, as causing LS. Case presentation We report on three siblings from an Iranian consanguineous family who presented with dwarfism. Whole-exome sequencing (WES) was performed on the proband, revealing a novel homozygous missense variant in the GHR gene (NM_000163.5; c.610 T > A, p.(Trp204Arg)) classified as a likely pathogenic variant according to the recommendation of the American College of Medical Genetics (ACMG). Co-segregation analysis was investigated using Sanger sequencing. Conclusions To date, approximately 400–500 LS cases with GHR biallelic variants, out of them 10 patients originating from Iran, have been described in the literature. Given the high rate of consanguineous marriages in the Iranian population, the frequency of LS is expected to be higher, which might be explained by undiagnosed cases. Early diagnosis of LS is very important, as treatment is available for this condition.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report

Bitarafan,

Khodaeian,

Garrousi

et al. 2023

BMC Endocr Disord

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Pathogenic Copy Number and Sequence Variants in Children Born SGA With Short Stature Without Imprinting Disorders

Hara-Isono

Nakamura

Fuke

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Children born small-for-gestational-age with short stature (SGA-SS) is associated with (epi) genetic defects, including imprinting disorders (IDs), pathogenic copy number variants (PCNVs), and pathogenic variants of genes involved in growth. However, comprehensive studies evaluating these three factors are very limited. Objective To clarify the contribution of PCNVs and candidate pathogenic variants to SGA-SS. Design Comprehensive molecular analyses consisting of methylation analysis, copy number analysis, and multigene sequencing. Patients and Methods We enrolled 140 patients referred to us for genetic testing for SGA-SS. Among them, we excluded 42 patients meeting Netchine-Harbison clinical scoring system criteria for Silver-Russell syndrome (SRS) and four patients with abnormal methylation levels of the IDs-related differentially methylated regions. Consequently, we conducted copy number analysis and multigene sequencing for 86 SGA-SS patients with sufficient sample volume. We also evaluated clinical phenotypes of patients with PCNVs or candidate pathogenic variants. Results We identified eight (9.3%) and eleven (12.8%) patients with PCNVs and candidate pathogenic variants, respectively. According to the American College of Medical Genetics standards and guidelines, five variants were classified as pathogenic and the remaining six variants were classified as variants of unknown significance. Genetic diagnosis was made in twelve patients. All patients with PCNVs or candidate pathogenic variants did not correspond perfectly to characteristic clinical features of each specific genetic cause. Conclusion We clarified the contribution of PCNVs and pathogenic variants to SGA-SS without IDs. Comprehensive molecular analyses, including copy number analysis and multigene sequencing, should be considered for patients with unknown SGA-SS etiology.

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A case report and literature review of monoallelic mutation of GHR

Cited by 2 publications

References 8 publications

Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report

Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report

Pathogenic Copy Number and Sequence Variants in Children Born SGA With Short Stature Without Imprinting Disorders

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