Two Novel Variants and One Previously Reported Variant in the Insulin Receptor Gene in Two Cases with Severe Insulin Resistance Syndrome

• Published in: Molecular syndromology 2020-06, Vol.11 (2), p.90-96
• Main Authors: Dagdeviren Cakir, Aydilek, Saidov, Said, Turan, Hande, Ceylaner, Serdar, Özer, Yavuz, Kutlu, Tufan, Ercan, Oya, Evliyaoglu, Olcay
• Format: Article
• Language: English
• Subjects: Novel Insights from Clinical Practice
• ISSN: 1661-8769; 1661-8777
• DOI: 10.1159/000506722

Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS) are rare diseases caused by biallelic variants within the insulin receptor gene (INSR). Here, we report 2 cases: one with DS and the other with RMS. The case with DS presented with intrauterine growth retardation, nipple hypertrophy, clitoromegaly, distended abdomen, hypertrichosis, and dysmorphic features. The second case showed severe acanthosis nigricans, hyperkeratosis, and hypertrichosis. In both cases, abnormal glucose homeostasis due to severe insulin resistance was observed. The diagnosis of DS and RMS was established based on clinical characteristics, abnormal glucose homeostasis, high serum insulin levels, and determination of pathogenic variants in the INSR gene. The first case with DS has 2 novel homozygous variants, NM_000208.3, c.3122delA (p.N1041Mfs*16) and c.3419C>G (p.A1140G), and the second case with RMS has a previously reported homozygous variant NM_000208.3, c.3529+5G>A (IVS19+5G>A) in the INSR gene.