A Novel Mutation in the INSR Gene Causes Severe Insulin Resistance and Rabson-Mendenhall Syndrome in a Paraguayan Patient.

Autor: Rojas Velazquez MN; Department of Pediatrics, University Children's Hospital Bern, Inselspital, 3010 Bern, Switzerland.; Translational Hormone Research Program, Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3010 Bern, Switzerland., Blanco F; Facultad de Ciencias Médicas, Universidad Nacional de Asunción, Asunción 111241, Paraguay.; Instituto de Previsión Social, Asunción 172755, Paraguay., Ayala-Lugo A; Laboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, Paraguay., Franco L; Laboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, Paraguay., Jolly V; Laboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, Paraguay., Di Tore D; Laboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, Paraguay., Martínez de Lapiscina I; Department of Pediatrics, University Children's Hospital Bern, Inselspital, 3010 Bern, Switzerland.; Translational Hormone Research Program, Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland., Janner M; Department of Pediatrics, University Children's Hospital Bern, Inselspital, 3010 Bern, Switzerland., Flück CE; Department of Pediatrics, University Children's Hospital Bern, Inselspital, 3010 Bern, Switzerland.; Translational Hormone Research Program, Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland., Pandey AV; Department of Pediatrics, University Children's Hospital Bern, Inselspital, 3010 Bern, Switzerland.; Translational Hormone Research Program, Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Mar 08; Vol. 25 (6). Date of Electronic Publication: 2024 Mar 08.
DOI: 10.3390/ijms25063143
Abstrakt: Rabson-Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report the first case of RMS in a Paraguayan patient. The patient is a 6-year-old girl who presented with hypertrichosis, acanthosis nigricans, nephrocalcinosis, and elevated levels of glucose and insulin that served as diagnostic indicators for RMS. Genetic testing by next-generation sequencing (NGS) revealed two pathogenic variants in exons 2 and 19 of the INSR gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel INSR c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software programs predicted it as pathogenic. The c.3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and RMS. The management of RMS is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of RMS to the Paraguayan population and adds a novel pathogenic variant to the existing literature.
Databáze: MEDLINE
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