One Novel 2.43Kb Deletion and One Single Nucleotide Mutation of the INSR Gene in a Chinese Neonate with Rabson-Mendenhall Syndrome
Xiang Chen1, Huijun Wang2, Bingbing Wu2, Xinran Dong2, Bo Liu2, Hongbo Chen2, Yulan Lu2, Wenhao Zhou3, Lin Yang41Children’s Hospital of Fudan University, Clinic of Neonatology, Shanghai, China2Children’s Hospital of Fudan University, Key Laboratory of Birth Defects, Shanghai, China
3Children’s Hospital of Fudan University, Clinic of Neonatology, Shanghai, China & Children’s Hospital of Fudan University, Key Laboratory of Birth Defects, Shanghai, China
4Children’s Hospital of Fudan University, Key Laboratory of Birth Defects, Shanghai, China & Children’s Hospital of Fudan University, Clinic of Endocrinology, Genetics and Metabolic Diseases, Shanghai, China
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.
Manuscript Language: English
