A Novel Mutation in the <i>INSR</i> Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient

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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:International Journal of Molecular Sciences
Subjects:
Rabson–Mendenhall syndrome
insulin resistance
diabetes mellitus
acanthosis nigricans
tyrosine kinase
insulin
Online Access:https://www.mdpi.com/1422-0067/25/6/3143
Description
Summary: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.
ISSN:1661-6596
1422-0067

Similar Items