info:eu-repo/semantics/article
Type A Insulin Resistance Syndrome- Novel insulin receptor gene mutation and familiar phenotypic variability
Date
2019-06Registration in:
Freire, Analia; Scaglia, Paula Alejandra; Gryngarten, Mirta Graciela; Gutiérrez, Mariana Lilián; Arcari, Andrea Josefina; et al.; Type A Insulin Resistance Syndrome- Novel insulin receptor gene mutation and familiar phenotypic variability; Peertechz Publications; International Journal of Clinical Endocrinology and Metabolism; 5; 6-2019; 17-19
2640-7582
CONICET Digital
CONICET
Author
Freire, Analia
Scaglia, Paula Alejandra
Gryngarten, Mirta Graciela
Gutiérrez, Mariana Lilián
Arcari, Andrea Josefina
Suarez, Laura
Ballerini, Maria Gabriela
Valinotto, Laura Elena
Natale, Mónica Inés
Del Toro Camargo, Kenny
Bergada, Cesar
Rey, Rodolfo Alberto
Ropelato, Maria Gabriela
Abstract
Type A Insulin Resistance Syndrome is due to heterozygous mutations in the insulin receptor (INSR) gene or its signaling pathway. We present a premenarcheal 14 year-old girl with normal BMI, severe hirsutism, acanthosis nigricans, clitoral hypertrophy, deep voice, enlarged polycystic ovaries, severe hyperinsulinemia and biochemical hyperandrogenism.We identifi ed a novel heterozygous missense variant in the tyrosine kinase domain of INSR(p.Leu1150Pro) and an heterozygous missense variant in SH2B adapter protein 1 involved in the insulin pathway (p.Ala663Val). Interestingly, the patients? mother and brother had the same INSR mutation although of a milder phenotype, reason why their IR went undiagnosed.The novel heterozygous p.Leu1150Pro mutation in the INSR gene appears to be the cause of the type A insulin resistance syndrome; the SH2B1 mutation, likely to synergistically affect the insulin pathway, may contribute to explain the more severe presentation of the phenotype in the patient and the phenotypic variability of the syndrome within this family.