One Novel 2.43Kb Deletion and One Single Nucleotide Mutation of the INSR Gene in a Chinese Neonate with Rabson-Mendenhall Syndrome

Abstract

Mutations in the insulin receptor (INSR) gene are responsible for Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). Insulin resistance is a feature of both diseases.Our patient was a Chinese neonate suffering from abnormal glucose homeostasis, hyperinsulinemia, dry skin, heavy hair, growth retardation and an elevated testosterone level. To search for candidate point mutations, small insertions or deletions and copy number variants, 2742 inherited disease-gene panel sequencing was performed. One pathogenic mutation (c.3355C>T, p.Arg1119Trp) and a novel 2.43Kb deletion (chr19:7150507-7152938) in INSR were found. The patient was diagnosed as RMS. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) confirmed the missense variant and microdeletion, respectively. We therefore supposed that these variants were candidate mutations in this case. We report a novel 2.43Kb deletion in INSR gene and provide further proof of the power of next generation sequencing in rare disease diagnosis.

Clinical and Functional Characterization of Novel INSR Variants in Two Families With Severe Insulin Resistance Syndrome

“…Patient 2,II.1 was compound heterozygous for the novel variant c.749_751del [p.(Thr250del)] and known variant c.3355C>T [p.(Arg1119Trp)], located in the α- and β-subunits, respectively. The p.Arg1119Trp variant was previously identified in patients with RMS (compound heterozygous with a 2.3kb microdeletion covering part of exon 10 and all of exon 11) and DS (compound heterozygous with p.Glu1206Lys in the β-subunit) ( 2 , 25 ). Another variant c.3556G>A [p.(Arg1119Gln)] at the same amino acid position was previously described in a homozygous patient with DS ( 26 ).…”