A novel homozygous missense mutation in the insulin receptor gene results in an atypical presentation of Rabson-Mendenhall syndrome

Abdelaziz, Rim Ben; Chehida, Amel Ben; Azzouz, Hatem; Boudabbous, Hela; Lascols, Olivier; Turkia, Hadhami Ben; Tebib, Néji

doi:10.1016/j.ejmg.2015.11.015

Cited by 11 publications

(10 citation statements)

References 9 publications

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“…However, not all mutations from that region lead to the most severe of manifestations, namely Donohue syndrome. In fact, a c.394G>A (p.Gly132Ser) mutation was associated with Rabson-Mendenhall syndrome [10] , and two other mutations, c.433C>T (p.Arg145Cys) [11] and c.438C>G (p.lle146Met) [12] , were found to cause autosomal recessive insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Homozygous INSR Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates

Bastaki

Nair²,

Mohamed³

et al. 2016

Horm Res Paediatr

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Background/Aims: This study aimed to identify, clinically and molecularly, the causality of Rabson-Mendenhall syndrome in an Emirati family. It is one of the monogenic syndromes of abnormal glucose homeostasis, which result from insulin receptor defects. Methods: A novel nonsynonymous variant in the INSR gene was uncovered by whole exome sequencing and confirmed using Sanger sequencing in the patient and his parents. Various in silico tools were utilized to analyze the functional consequences of the variant. Results: Results revealed a previously unreported INSR variant in the family: c.421C>T (p.Arg141Trp). Homozygosity for the variant was found in the patient, while both parents were heterozygous. Conclusion: The nonsynonymous protein change hit a highly conserved arginine residue in the insulin-binding α-subunit of the receptor and was deemed ‘functionally damaging' by a myriad of bioinformatics tools. This report is a step forward along the way of achieving a better molecular and clinical characterization of Rabson-Mendenhall syndrome.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Homozygous INSR Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates

Bastaki

Nair²,

Mohamed³

et al. 2016

Horm Res Paediatr

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“…Insulin as a potent anabolic hormone enhances cellular growth and proliferation. Accordingly, mutations of the insulin receptor result in growth retardation in humans [ 15 ]. Delayed hepatocellular mitotic progression and an impairment of liver regeneration has been reported for insulin receptor-expressing hepatocytes in Egr-1-deficient mice [ 13 ].…”

Section: Transcription Factors Under Control Of Insulin Receptor Signalingmentioning

confidence: 99%

Insulin-Responsive Transcription Factors

2021

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The hormone insulin executes its function via binding and activating of the insulin receptor, a receptor tyrosine kinase that is mainly expressed in skeletal muscle, adipocytes, liver, pancreatic β-cells, and in some areas of the central nervous system. Stimulation of the insulin receptor activates intracellular signaling cascades involving the enzymes extracellular signal-regulated protein kinase-1/2 (ERK1/2), phosphatidylinositol 3-kinase, protein kinase B/Akt, and phospholipase Cγ as signal transducers. Insulin receptor stimulation is correlated with multiple physiological and biochemical functions, including glucose transport, glucose homeostasis, food intake, proliferation, glycolysis, and lipogenesis. This review article focuses on the activation of gene transcription as a result of insulin receptor stimulation. Signal transducers such as protein kinases or the GLUT4-induced influx of glucose connect insulin receptor stimulation with transcription. We discuss insulin-responsive transcription factors that respond to insulin receptor activation and generate a transcriptional network executing the metabolic functions of insulin. Importantly, insulin receptor stimulation induces transcription of genes encoding essential enzymes of glycolysis and lipogenesis and inhibits genes encoding essential enzymes of gluconeogenesis. Overall, the activation or inhibition of insulin-responsive transcription factors is an essential aspect of orchestrating a wide range of insulin-induced changes in the biochemistry and physiology of insulin-responsive tissues.

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“…За повідомленням [15], 13-річна дівчинка наді-йшла зі скаргами на червонувате забарвлення скла-док тіла, що поступово збільшувалося, полідипсію й поліурію. Двоє з її братів і сестер померли в пери-натальному періоді.…”

Section: ключові слова: інсулінорезистентність; мутація гена рецепторunclassified

Особливий Випадок Інсулінорезистентності В Дівчинки 12 Років (Синдром Рабсона — Менденхолла)

Sorokman

Moldovan

Макарова

2021

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A novel homozygous missense mutation in the insulin receptor gene results in an atypical presentation of Rabson-Mendenhall syndrome

Cited by 11 publications

References 9 publications

Identification of a Novel Homozygous <b><i>INSR</i></b> Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates

Identification of a Novel Homozygous <b><i>INSR</i></b> Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates

Insulin-Responsive Transcription Factors

Особливий Випадок Інсулінорезистентності В Дівчинки 12 Років (Синдром Рабсона — Менденхолла)

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