Congenital Hyperinsulinism in Infants with Turner Syndrome: Possible Association with Monosomy X and KDM6A Haploinsufficiency
Autor: | Kara E. Boodhansingh, Diva D. De León, Pan Chen, Susan A. Becker, Charles A. Stanley, Tricia R. Bhatti, Changhong Li, Vaneeta Bamba, Laura K. Conlin, Christopher E Gibson, N. Scott Adzick, Arupa Ganguly |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Monosomy endocrine system diseases business.industry Endocrinology Diabetes and Metabolism Hypoglycemia medicine.disease 03 medical and health sciences 030104 developmental biology Endocrinology Internal medicine Pediatrics Perinatology and Child Health Turner syndrome medicine Congenital hyperinsulinism Haploinsufficiency business Hyperinsulinism Kabuki syndrome X chromosome |
Zdroj: | Hormone Research in Paediatrics. 89:413-422 |
ISSN: | 1663-2826 1663-2818 |
Popis: | Background: Previous case reports have suggested a possible association of congenital hyperinsulinism with Turner syndrome. Objective: We examined the clinical and molecular features in girls with both congenital hyperinsulinism and Turner syndrome seen at The Children’s Hospital of Philadelphia (CHOP) between 1974 and 2017. Methods: Records of girls with hyperinsulinism and Turner syndrome were reviewed. Insulin secretion was studied in pancreatic islets and in mouse islets treated with an inhibitor of KDM6A, an X chromosome gene associated with hyperinsulinism in Kabuki syndrome. Results: Hyperinsulinism was diagnosed in 12 girls with Turner syndrome. Six were diazoxide-unresponsive; 3 had pancreatectomies. The incidence of Turner syndrome among CHOP patients with hyperinsulinism (10 of 1,050 from 1997 to 2017) was 48 times more frequent than expected. The only consistent chromosomal anomaly in these girls was the presence of a 45,X cell line. Studies of isolated islets from 1 case showed abnormal elevated cytosolic calcium and heightened sensitivity to amino acid-stimulated insulin release; similar alterations were demonstrated in mouse islets treated with a KDM6A inhibitor. Conclusion: These results demonstrate a higher than expected frequency of Turner syndrome among children with hyperinsulinism. Our data suggest that haploinsufficiency for KDM6A due to mosaic X chromosome monosomy may be responsible for hyperinsulinism in Turner syndrome. |
Databáze: | OpenAIRE |
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