Multidrug therapy in a patient with Rabson–Mendenhall syndrome

Moreira, Rodrigo O.; Zagury, Roberto Luís; Nascimento, T. S.; Zagury, Leão

doi:10.1007/s00125-010-1879-5

Cited by 25 publications

(20 citation statements)

References 7 publications

(8 reference statements)

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“…Cases 5 and 6, which lacked INSR mutations, developed fatty liver, which indicates a pathogenic mechanism other than INSR dysfunction, such as a lipid metabolism defect. All patients with INSR mutations received metformin, which normalized HbA1c within 1 year, indicating partial improvement of glycometabolism during adolescence, as reported previously …”

Section: Resultsmentioning

confidence: 53%

Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β‐subunit of the insulin receptor (INSR) gene

Takasawa

Tsuji‐Hosokawa

Takishima

et al. 2018

Journal of Diabetes

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Section: Resultsmentioning

confidence: 53%

Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β‐subunit of the insulin receptor (INSR) gene

Takasawa

Tsuji‐Hosokawa

Takishima

et al. 2018

Journal of Diabetes

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“…1,4 The extreme insulin resistance in RMS leads eventually to progressive beta cell dysfunction and hyperglycemia with ketoacidosis. [7][8][9][10][11][12][13][14][15][16][17] The three homozygous mutations previously identified in RMS fall in the alpha subunit of the receptor. 2,5,6 Genetic analysis in the present patient revealed a previously undescribed mutation in the insulin receptor gene, p.Ile321Phe.…”

Section: Discussionmentioning

confidence: 99%

Rabson–Mendenhall syndrome with recurrent cerebral infarcts caused by a novel INSR mutation

et al. 2013

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Rabson-Mendenhall syndrome (RMS) is an autosomal recessive disorder characterized by extreme insulin resistance and certain characteristic phenotypic features. The primary defect lies in the insulin receptor and involves biallelic mutations that lead to a loss of function through various postulated defects. We present a 9-year-old female patient with RMS complicated by multiple cerebral infarcts, in whom genetic analysis revealed a novel insulin receptor mutation.

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“…These mutations are present in either the extracellular ligand-binding domain or the intracellular phosphorylation domain encoded by the INSR (Table 2) [3,4,[12][13][14][15][16][17][18][19][20][21]. These mutations can directly affect the number of mature receptors present on a cell, the affinity of these receptors for binding of insulin, and/or tyrosine kinase activity.…”

Section: Signaling Pathwaysmentioning

confidence: 99%

Functional characterization of insulin receptor gene mutations contributing to Rabson-Mendenhall syndrome - phenotypic heterogeneity of insulin receptor gene mutations

et al. 2011

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Rabson-Mendenhall syndRoMe (RMS)is a rare disorder involving severe insulin resistance due to mutations present in the insulin receptor (INSR) gene [1,2]. This syndrome usually has marked hyperinsulinemia and profound insulin-resistance diabetes [3]. Additional characteristics of RMS can include intrauterine and postnatal growth retardation, acanthosis nigricans, hypertrichosis, dental precocity, thick nails, pineal hyperplasia, genital enlargement in both males and females, abdominal distension, and other distinctive dysmorphic features [4,5] (INSR). A Chinese girl with RMS presented with profound diabetes, hyperinsulinemia, acanthosis nigricans, hirsutism, and abnormalities of teeth and nails. Direct sequencing of the patient's INSR detected heterozygote mutations at Arg83Gln (R83Q) and Ala1028Val (A1028V), with the former representing a novel mutation. Functional studies of Chinese hamster ovary (CHO) cells transfected with wild-type (WT) and mutant forms of INSR were performed to evaluate the effects of these mutations on receptor expression and activation. Receptor expression, insulin binding activity, and phosphorylation of the R83Q variant were comparable to WT. In contrast, expression of the A1028V receptor was much lower than that of WT INSR, and impairment of insulin binding and autophosphorylation were nearly commensurate with the decrease in expression detected. Reductions in the phosphorylation of IRS-1, Akt, and Erk1/2 (60%, 40%, and 50% of WT, respectively) indicate that the A1028V receptor contributes to impaired signal transduction. In conclusion, INSR mutations associated with RMS were identified. Moreover, the A1028V mutation associated with a decrease in expression of INSR potentially accounts for loss of function of the INSR.Key words: Insulin receptor, Insulin resistance, Mutation, Rabson-Mendenhall syndrome ferent mutations in the INSR gene have been reported in patients with RMS. However, a clear genotype-phenotype correlation has not been established due of the paucity of investigations of these mutations in vitro or in vivo. In the present study, an 11-year-old patient with RMS attributable to compound heterozygous mutations in the INSR gene is presented. These mutations were assessed for their affect on INSR function. Patients and Methods SubjectsThe proband (RMS-1) was an 11-year-old Chinese girl, and the only child of healthy parents who had no family history of diabetes mellitus or other hereditary diseases. Written informed consent was obtained from the parents of the patient and from all control subjects recruited for genetic and physiological studies performed. The protocol for this study was in accordance with the Declaration of Helsinki and approved by the local ethical committee.

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Multidrug therapy in a patient with Rabson–Mendenhall syndrome

Cited by 25 publications

References 7 publications

Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β‐subunit of the insulin receptor (INSR) gene

Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β‐subunit of the insulin receptor (INSR) gene

Rabson–Mendenhall syndrome with recurrent cerebral infarcts caused by a novel INSR mutation

Functional characterization of insulin receptor gene mutations contributing to Rabson-Mendenhall syndrome - phenotypic heterogeneity of insulin receptor gene mutations

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