Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.
Heterozygous activating mutations in the KCNJ11 gene encoding the pore-forming Kir6.2 subunit of the pancreatic beta cell K(ATP) channel are the most common cause of permanent neonatal diabetes (PNDM). Patients with PNDM due to a heterozygous activating mutation in the ABCC8 gene encoding the SUR1 r...
| Main Authors: | , , , , , , , , , , , , , , |
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| 格式: | Journal article |
| 語言: | English |
| 出版: |
2007
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| _version_ | 1826296500333838336 |
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| author | Ellard, S Flanagan, SE Girard, C Patch, A Harries, L Parrish, A Edghill, E Mackay, D Proks, P Shimomura, K Haberland, H Carson, D Shield, J Hattersley, A Ashcroft, F |
| author_facet | Ellard, S Flanagan, SE Girard, C Patch, A Harries, L Parrish, A Edghill, E Mackay, D Proks, P Shimomura, K Haberland, H Carson, D Shield, J Hattersley, A Ashcroft, F |
| author_sort | Ellard, S |
| collection | OXFORD |
| description | Heterozygous activating mutations in the KCNJ11 gene encoding the pore-forming Kir6.2 subunit of the pancreatic beta cell K(ATP) channel are the most common cause of permanent neonatal diabetes (PNDM). Patients with PNDM due to a heterozygous activating mutation in the ABCC8 gene encoding the SUR1 regulatory subunit of the K(ATP) channel have recently been reported. We studied a cohort of 59 patients with permanent diabetes who received a diagnosis before 6 mo of age and who did not have a KCNJ11 mutation. ABCC8 gene mutations were identified in 16 of 59 patients and included 8 patients with heterozygous de novo mutations. A recessive mode of inheritance was observed in eight patients with homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present. |
| first_indexed | 2024-03-07T04:17:18Z |
| format | Journal article |
| id | oxford-uuid:c9d1c1a6-9224-4b8c-bef1-cc6901aab42e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:17:18Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:c9d1c1a6-9224-4b8c-bef1-cc6901aab42e2022-03-27T07:02:38ZPermanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c9d1c1a6-9224-4b8c-bef1-cc6901aab42eEnglishSymplectic Elements at Oxford2007Ellard, SFlanagan, SEGirard, CPatch, AHarries, LParrish, AEdghill, EMackay, DProks, PShimomura, KHaberland, HCarson, DShield, JHattersley, AAshcroft, FHeterozygous activating mutations in the KCNJ11 gene encoding the pore-forming Kir6.2 subunit of the pancreatic beta cell K(ATP) channel are the most common cause of permanent neonatal diabetes (PNDM). Patients with PNDM due to a heterozygous activating mutation in the ABCC8 gene encoding the SUR1 regulatory subunit of the K(ATP) channel have recently been reported. We studied a cohort of 59 patients with permanent diabetes who received a diagnosis before 6 mo of age and who did not have a KCNJ11 mutation. ABCC8 gene mutations were identified in 16 of 59 patients and included 8 patients with heterozygous de novo mutations. A recessive mode of inheritance was observed in eight patients with homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present. |
| spellingShingle | Ellard, S Flanagan, SE Girard, C Patch, A Harries, L Parrish, A Edghill, E Mackay, D Proks, P Shimomura, K Haberland, H Carson, D Shield, J Hattersley, A Ashcroft, F Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. |
| title | Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. |
| title_full | Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. |
| title_fullStr | Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. |
| title_full_unstemmed | Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. |
| title_short | Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. |
| title_sort | permanent neonatal diabetes caused by dominant recessive or compound heterozygous sur1 mutations with opposite functional effects |
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