Leprechaunism (Donohue syndrome): A case bearing novel compound heterozygous mutations in the insulin receptor gene

Kawashima, Yuki; Nishimura, R.; Utsunomiya, Akari; Kagawa, Reiko; Funata, Hiroaki; Fujimoto, Masanobu; Hanaki, Keiichi; Kanzaki, Sho

doi:10.1507/endocrj.ej12-0289

Cited by 26 publications

(25 citation statements)

References 14 publications

(12 reference statements)

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“…To evaluate the effect of insulin signaling defects during the fetal period, we compared the SDSs of birth weight between patients with Donohue syndrome (DS), Rabson–Mendenhall syndrome (RMS), and Type A IR. In addition to the present cases, we collected perinatal information for 12 Japanese patients (five with Type A IR and seven with DS or RMS) and 28 patients from other countries (two with Type A IR, 15 with DS, and 11 with RMS) based on previous studies . All birth weight SDSs for all nine patients with Type A IR were < 0 (mean [±SD] –1.65 ± 0.85; range from −0.72 to −3.28).…”

Section: Resultsmentioning

confidence: 99%

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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: 99%

“…To assess correlations between phenotype severity and birth weight, perinatal information was collected for patients with genetically proven SIR from previous reports . Birth weight SDSs were calculated based on a Japanese reference and international standard .…”

Section: Methodsmentioning

confidence: 99%

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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“…Metformin or thiazolidinediones have beneficial effects in some cases, but no comparative studies exist in severe insulin resistance [6]. It is well known that the insulin and IGF receptors are structurally related and share common postreceptor signaling pathways [12]. Thus, administrating recombinant human IGF-1 treatment for Donohue syndrome might rescue the defective INSR insulin pathway by enhancing insulin sensitivity through postreceptor cross-talk between insulin and IGF-1 signaling pathways [6,23,24].…”

Section: Discussionmentioning

confidence: 99%

“…However, 87.5% of mutations identified in Rabson-Mendenhall syndrome are missense mutations (7 of 8 mutations). Functional analyses of the INSR gene reveal that the disease phenotype is directly correlated with the severity of the gene mutation [2,11,12]. However, a clear genotype-phenotype correlation has not been established due to the rarity of this syndrome and the paucity of in vitro investigations.…”

Section: Introductionmentioning

confidence: 99%

Identification and Functional Characterization of Two Novel Nonsense Mutations in the β-Subunit of <b><i>INSR</i></b> That Cause Severe Insulin Resistance Syndrome

Choi

Kang²,

Kim³

et al. 2015

Horm Res Paediatr

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Background/Aims: Donohue syndrome is an extremely rare autosomal recessive disorder caused by mutations in INSR. This study describes the clinical course of a patient with Donohue syndrome, and we also evaluated the molecular and functional characteristics of 2 novel INSR mutations. Methods: Our patient was a male newborn with acanthosis nigricans, lack of subcutaneous fat, hirsutism, thick lips, and high serum insulin levels, all of which are characteristic of Donohue syndrome. INSR mutation analysis was performed, and Western blot analysis was used to verify the effects of the novel mutations on INSR protein expression. Results: Direct INSR sequencing identified the following 2 novel compound heterozygous mutations in the β-subunit of INSR: p.Arg1066* and p.Gln1232*. Western blot analysis of skin fibroblasts revealed a comparable expression of the α-subunit of INSR in mutant and control samples, but reduced levels of mature INSR β-subunit protein were found in mutant INSR-expressing cells in comparison to the controls. Conclusions: This study describes the clinical course of a male patient with Donohue syndrome and the molecular characteristics of 2 novel compound heterozygous mutations in INSR. These novel nonsense mutations are associated with reduced expression of the mature INSR β-subunit, which was most likely due to impaired proreceptor processing.

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“…It is well known that the insulin and IGF-1 receptors are structurally related and share common post-receptor signaling pathways (5, 6). Therefore, exogenous administration of recombinant human IGF-1 (rh-IGF-1) has been used in patients with leprechaunism (3, 7,8,9,10,11). However, there are few reports on the long-term effects of rh-IGF-1 and clinical course of leprechaunism.…”

Section: Introductionmentioning

confidence: 99%

Development of Endometrial Carcinoma in a Patient with Leprechaunism (Donohue Syndrome)

Sudo

Nakamura

et al. 2013

Clin Pediatr Endocrinol

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Leprechaunism is a rare autosomal recessive disease that is characterized by severe insulin resistance. This disease is caused by a defective insulin receptor and features abnormal glucose metabolism and retarded intrauterine and postnatal growth. However, there are few reports on the long-term course of leprechaunism. We reported the long-term clinical course and rh-IGF-1 treatment in a patient with leprechaunism. During follow-up her diabetes gradually deteriorated despite of treatment of rh-IGF-1. Furthermore, she developed endometrioid adenocarcinoma at the age of 24 yr. The development of endometrial disease must be carefully followed up in this disease.

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Leprechaunism (Donohue syndrome): A case bearing novel compound heterozygous mutations in the insulin receptor gene

Cited by 26 publications

References 14 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

Identification and Functional Characterization of Two Novel Nonsense Mutations in the β-Subunit of <b><i>INSR</i></b> That Cause Severe Insulin Resistance Syndrome

Development of Endometrial Carcinoma in a Patient with Leprechaunism (Donohue Syndrome)

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