A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient
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 nigr...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3143 |
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| author | Maria Natalia Rojas Velazquez Fabiola Blanco Ana Ayala-Lugo Lady Franco Valerie Jolly Denisse Di Tore Idoia Martínez de Lapiscina Marco Janner Christa E. Flück Amit V. Pandey |
| author_facet | Maria Natalia Rojas Velazquez Fabiola Blanco Ana Ayala-Lugo Lady Franco Valerie Jolly Denisse Di Tore Idoia Martínez de Lapiscina Marco Janner Christa E. Flück Amit V. Pandey |
| author_sort | Maria Natalia Rojas Velazquez |
| collection | DOAJ |
| description | 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 <i>INSR</i> gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel <i>INSR</i> 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. |
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| language | English |
| last_indexed | 2024-04-24T18:12:03Z |
| publishDate | 2024-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1a966dda846b4c77a79ad9bbe8da962d2024-03-27T13:45:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256314310.3390/ijms25063143A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan PatientMaria Natalia Rojas Velazquez0Fabiola Blanco1Ana Ayala-Lugo2Lady Franco3Valerie Jolly4Denisse Di Tore5Idoia Martínez de Lapiscina6Marco Janner7Christa E. Flück8Amit V. Pandey9Department of Pediatrics, University Children’s Hospital Bern, Inselspital, 3010 Bern, SwitzerlandFacultad de Ciencias Médicas, Universidad Nacional de Asunción, Asunción 111241, ParaguayLaboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, ParaguayLaboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, ParaguayLaboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, ParaguayLaboratorio de Genética Molecular, Departamento de Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción 111241, ParaguayDepartment of Pediatrics, University Children’s Hospital Bern, Inselspital, 3010 Bern, SwitzerlandDepartment of Pediatrics, University Children’s Hospital Bern, Inselspital, 3010 Bern, SwitzerlandDepartment of Pediatrics, University Children’s Hospital Bern, Inselspital, 3010 Bern, SwitzerlandDepartment of Pediatrics, University Children’s Hospital Bern, Inselspital, 3010 Bern, SwitzerlandRabson–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 <i>INSR</i> gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel <i>INSR</i> 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.https://www.mdpi.com/1422-0067/25/6/3143Rabson–Mendenhall syndromeinsulin resistancediabetes mellitusacanthosis nigricanstyrosine kinaseinsulin |
| spellingShingle | Maria Natalia Rojas Velazquez Fabiola Blanco Ana Ayala-Lugo Lady Franco Valerie Jolly Denisse Di Tore Idoia Martínez de Lapiscina Marco Janner Christa E. Flück Amit V. Pandey A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient International Journal of Molecular Sciences Rabson–Mendenhall syndrome insulin resistance diabetes mellitus acanthosis nigricans tyrosine kinase insulin |
| title | A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient |
| title_full | A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient |
| title_fullStr | A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient |
| title_full_unstemmed | A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient |
| title_short | A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient |
| title_sort | novel mutation in the i insr i gene causes severe insulin resistance and rabson mendenhall syndrome in a paraguayan patient |
| topic | Rabson–Mendenhall syndrome insulin resistance diabetes mellitus acanthosis nigricans tyrosine kinase insulin |
| url | https://www.mdpi.com/1422-0067/25/6/3143 |
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