Insulin receptor gene mutations in a patient: A story from hyperinsulinism to molecular understanding of Leprechaunism (Donohue) syndrome
- سال انتشار: 1398
- محل انتشار: اولین همایش علوم پایه دربیماریهای ارثی کودکان
- کد COI اختصاصی: BSIPD01_025
- زبان مقاله: انگلیسی
- تعداد مشاهده: 441
نویسندگان
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular sciences institute, Tehran university medical sciences, Tehran, Iran
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular sciences institute, Tehran university medical sciences, Tehran, Iran
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular sciences institute, Tehran university medical sciences, Tehran, Iran
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular sciences institute, Tehran university medical sciences, Tehran, Iran
چکیده
Donohue syndrome (Leprechaunism) is an autosomal recessive genetic disorder characterized by severe insulin resistance, a condition in which the body s tissues and organs do not respond properly to the insulin hormone. The mutations responsible for the disorder are found on the short arm chromosome 19 (19p13.2) within the coding sequence of the INSR gene (insulin receptor) causing the production of inactive receptor molecules. The mutation of the INSR gene reduces the number of insulin receptors that reach the cell membrane or disrupt the function of these receptors. This syndrome is characterized by severe insulin resistance, hyperinsulinemia, postprandial hyperglycemia, pre-prandial hypoglycemia, intrauterine and postnatal growth retardation, dysmorphic findings, and clinical and laboratory findings of hyper-androgenemia due to homozygous or compound heterozygous inactivating mutations in the insulin receptor gene. Abnormalities also have been found in the thymus, pituitary gland, liver, and kidneys.Materials & Methods: We present a case of Donohue syndrome owing to the rarity of this syndrome (1 case in every million births). The case was a 1-month-old Persian female, for consanguineous parents. She was admitted in endocrinology and metabolism research institute, Tehran, Iran, for facial dysmorphic feature and extremely high insulin level (> 1000 mg/dl) soon after birth that leading to a clinical diagnosis of Hyperinsulinism. Delivery was at 36 weeks, and birth weight was 2200 g. INSR gene molecular analysis was performed by Sanger sequencing.Results: Genetic analysis revealed a homozygous nonsense mutation p.Arg813Ter was found, located in the exon 12 of INSR gene. This previously reported mutation is predicted to be pathogenic and this result confirms a diagnosis of Donohue syndrome due to a homozygous mutation in the INSR gene.Conclusion & discussion: There is a scarcity of genetic information on Donohue among the Iranian population. Consanguinity is one of underlying reasons for the appearance of rare genetic disorders. Genetic counseling and overwhelming the alertness of the negative consequences of consanguinity on public health are warranted.کلیدواژه ها
Donohue syndrome, Leprechaunism, INSR gene, hyperinsulinism, sequencingمقالات مرتبط جدید
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