Chromosome 11p15 Paternal Isodisomy in Focal Forms of Neonatal Hyperinsulinism
Autor: | P de Lonlay, Serge Romana, F. Jaubert, C. Werl, C. Bellanné-Chantelot, V. Verkarre, Laurence Hubert, M. le Lorch, Claire Nihoul-Fékété, Lena Damaj, Y de Keyzer, Y. Aigrain |
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Rok vydání: | 2008 |
Předmět: |
Male
medicine.medical_specialty Non-Mendelian inheritance Receptors Drug Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) Biology Sulfonylurea Receptors medicine.disease_cause Biochemistry Fathers Endocrinology Hyperinsulinism Insulin-Secreting Cells Internal medicine Gene duplication medicine Humans Potassium Channels Inwardly Rectifying Allele Alleles In Situ Hybridization Fluorescence Genetics Mutation Ploidies Chromosomes Human Pair 13 Reverse Transcriptase Polymerase Chain Reaction Chromosomes Human Pair 11 Biochemistry (medical) Infant Newborn Chromosome DNA Uniparental Disomy medicine.disease Immunohistochemistry Congenital hyperinsulinism ATP-Binding Cassette Transporters Microsatellite Repeats |
Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 93:4941-4947 |
ISSN: | 1945-7197 0021-972X |
Popis: | Focal forms of congenital hyperinsulinism are due to a constitutional heterozygous mutation of paternal origin in the ABCC8 gene, more often than the KCNJ11 gene, located in the 11p15.1 region. This mutation is associated with the loss of the maternally inherited 11p15.1 to 11p15.5 region in the lesion. We investigated the possible occurrence of a compensatory duplication of the paternal 11p15.1-11p15.5 region.A combined immunohistochemistry and fluorescent in situ hybridization study on beta-cell interphase nuclei with probes covering two genes located in this region (ABCC8 and CDKN1C genes) was performed in four cases of focal forms of hyperinsulinism.beta-Cells in the lesions of four cases of focal congenital hyperinsulinism were diploid for chromosomes 11 and 13. The 11p15.1 to 11p15.2 and 11p15.4 to 11p15.5 regions containing ABCC8 and CDKN1C genes, respectively, were present with two copies. Loss of the maternal allele was confirmed in these focal lesions with microsatellite markers flanking the ABCC8 and CDKN1C genes, whereas a heterozygous mutation in the ABCC8 gene was inherited from the father.There is a duplication of the paternal allele on chromosome 11 in the focal forms of hyperinsulinism lesion. The paternal isodisomy observed rendered the beta-cells homozygous for ABCC8 mutation and harbored a K-channel defect in the lesion similar to that observed in diffuse forms of congenital hyperinsulinism. |
Databáze: | OpenAIRE |
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