Rabson-Mendenhall syndrome caused by a novel splice-site mutation (c.1123+2 T>C) of insulin receptor: A case report and review of literature.

BACKGROUND

Rabson-Mendenhall syndrome (RMS) is an extremely rare monogenic form of diabetes caused by mutations in the insulin receptor (INSR) gene, with only about 50 cases reported worldwide to date. Here, we report a case of RMS caused by a previously unreported c.1123+2 T>C splice mutation.

CASE SUMMARY: The patient was diagnosed with acanthosis nigricans and hypertrichosis at birth, and the growth rate was slower than that of normal children. At age 5, the patient had severe hyperinsulinemia, congenital heart abnormalities, and pineal cysts. At age 13, he was diagnosed with diabetes and exhibited symptoms of hyperinsulinemia, low body weight, growth retardation, acanthosis nigricans, dental anomalies, an oversized penis, and a pineal cyst. Sequencing results indicated an INSR c.1123+2 T>C mutation, and bioinformatic analysis suggested that this mutation led to splicing abnormalities, thereby affecting INSR function. Both parents carried the mutated gene, whereas his brother had a normal genotype.

CONCLUSION

Genetic diagnosis is vital in RMS; c.1123+2 T>C mutation of INSR causes pancreatic decline; current treatments show limited effectiveness.