A Case Report: Treatment, follow-up, and literature review of type A insulin resistance syndrome caused by a De Novo INSR c.3328G>C mutation
Abstract
Background: Type A insulin resistance syndrome (TAIRS) is a rare inherited disorder caused by mutations in the insulin receptor (INSR) gene. It is characterized by severe insulin resistance, hyperandrogenism, and acanthosis nigricans. Its clinical manifestations overlap with those of polycystic ovary syndrome (PCOS), making it prone to misdiagnosis, particularly in adolescent females. Currently, the diagnosis of TAIRS relies on clinical evaluation and genetic confirmation, while long-term management strategies remain limited and challenging.
Case presentation: We report a 12-year-old female proband who presented with severe hyperinsulinemia, hyperandrogenism (hirsutism), acanthosis nigricans, and polycystic ovarian changes despite a non-obese phenotype. Whole-exome sequencing identified a de novo heterozygous variant in the INSR gene (NM_000208.4:c.3328G>C, p.Asp1110His). This variant was absent from the ClinVar and gnomAD databases and was predicted to be deleterious by in silico analyses. Family segregation analysis demonstrated that neither parent nor the proband's brother carried the variant, consistent with a de novo event. According to ACMG guidelines, this variant was classified as "likely pathogenic," providing a molecular basis for the diagnosis of TAIRS.
Conclusions: This case is attributed to a de novo p.Asp1110His variant in INSR. The diagnostic process highlights the importance of genetic testing in adolescents presenting with atypical PCOS features,…
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