Details

Autor(en) / Beteiligte

• Qin, Litao
• Li, Xiaobo
• Hou, Qiaofang
• Wang, Hongdan
• Lou, Guiyu
• Li, Tao
• Wang, Li
• Liu, Hongyan
• Li, Xichuan
• Liao, Shixiu

Titel

Novel heterozygous mutations of the INSR gene in a familial case of Donohue syndrome

Ist Teil von

• Clinica chimica acta, 2017-10, Vol.473, p.26-31

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2017

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Donohue syndrome (DS), a rare autosomal recessive disease which represents severe insulin resistance, pre- and postnatal growth retardation, hypertrichosis, and dysmorphic features, is caused by mutations in the insulin receptor (INSR) gene. Here, we have reported the clinical, molecular, and biochemical characterizations of a patient with DS. In this article, we have also reported a case with 2 novel INSR mutations and the DS phenotype. Using next-generation sequencing (NGS), we screened 27 known genes involved in inherited maturity-onset diabetes of the young (MODY) and identified compound heterozygous mutations in the INSR gene in the patient with DS, c.62T>G (p.L21R) and c.2563G>T (p.V855F). The positive correlation of these mutations with DS was further validated by Sanger DNA sequencing of his lineal consanguinity, indicating that these pathogenic mutations were inherited maternally and paternally, respectively. Therefore, our finding expanded the number of reported cases of this rare disease and the mutation spectrum of INSR mutation, suggesting that NGS is an accurate, rapid, and cost-effective method for the genetic diagnosis of this rare disease. •Donohue syndrome (DS) is a very rare autosomal recessive (AR) disease affecting less than one in one million live births. Here, we have reported the clinical, molecular, and biochemical characterizations of a patient with DS.•Using NGS, we identified compound heterozygous mutations in the INSR gene in the patient with DS. This is the first report on the use of NSG to perform a molecular diagnosis of DS.•The positive correlation of these mutations, c.62T>G (p.L21R) and c.2563G>T (p.V855F), with DS was further validated by Sanger DNA sequencing. As we known, these mutations were the first to be reported in INSR genes in an Asian population.