Clinical characteristics and long-term follow-up of patients with diabetes due to PTF1A enhancer mutations
dc.contributor.author | Demirbilek, H | |
dc.contributor.author | Cayir, A | |
dc.contributor.author | Flanagan, SE | |
dc.contributor.author | Yıldırım, R | |
dc.contributor.author | Kor, Y | |
dc.contributor.author | Gurbuz, F | |
dc.contributor.author | Haliloğlu, B | |
dc.contributor.author | Yıldız, M | |
dc.contributor.author | Baran, RT | |
dc.contributor.author | Akbas, ED | |
dc.contributor.author | Demira, M | |
dc.contributor.author | Ünal, E | |
dc.contributor.author | Arslan, G | |
dc.contributor.author | Vuralli, D | |
dc.contributor.author | Buyukyilmaz, G | |
dc.contributor.author | Al-Khawaga, S | |
dc.contributor.author | Saeed, A | |
dc.contributor.author | Al Maadheed, M | |
dc.contributor.author | Khalifa, A | |
dc.contributor.author | Onal, H | |
dc.contributor.author | Yuksel, B | |
dc.contributor.author | Ozbek, MN | |
dc.contributor.author | Bereket, A | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Hussain, K | |
dc.contributor.author | De Franco, E | |
dc.date.accessioned | 2020-09-02T12:09:13Z | |
dc.date.issued | 2020-09-07 | |
dc.description.abstract | Context: Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with loss-of-function PTF1A mutations. Their clinical phenotype and disease progression have not been well characterised. Objective: To evaluate phenotype and genotype characteristics and long-term follow78 up of patients with PTF1A enhancer mutations. Setting: Twelve tertiary paediatric endocrine referral centres. Patients: 30 patients with diabetes caused by PTF1A enhancer mutations. Median follow-up duration was 4 years. Main Outcome Measures: Presenting and follow-up clinical (birthweight, gestational age, symptoms, auxology) and biochemical (pancreatic endocrine and exocrine functions, liver function, glycated haemoglobin) characteristics, pancreas imaging, genetic analysis. Results: Five different homozygous mutations affecting conserved nucleotides in the PTF1A distal enhancer were identified. The commonest was the Chr10:g.23508437A>G mutation (n=18). Two patients were homozygous for the novel Chr10:g.23508336A>G mutation. Birthweight was often low (median SDS=-3.4). The majority of patients presented with diabetes soon after birth (median age of diagnosis:5 days). Only 2/30 presented after 6 months of age. All patients had exocrine pancreatic insufficiency. Five had developmental delay (4 mild) on long term follow-up. Previously undescribed common features in our cohort were: transiently elevated ferritin level (n=12/12 tested), anaemia (19/25) and cholestasis (14/24). Postnatal growth was impaired (median height SDS:- 2.35, median BMI SDS:-0.52 SDS) with 20/29 (69%) cases having growth retardation. Conclusion: We report the largest series of patients with diabetes caused by PTF1A enhancer mutations. Our results expand the disease phenotype, identifying recurrent extra-pancreatic features which likely reflect long-term intestinal malabsorption. | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.identifier.citation | Vol. 105 (12), article dgaa613 | |
dc.identifier.doi | 10.1210/clinem/dgaa613 | |
dc.identifier.grantnumber | 19/0005971 | en_GB |
dc.identifier.grantnumber | 098395/Z/12/Z | en_GB |
dc.identifier.grantnumber | 105636/Z/14/Z | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/122679 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press (OUP) / Endocrine Society | en_GB |
dc.rights | © Endocrine Society 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | |
dc.subject | PTF1A gene | en_GB |
dc.subject | permanent | en_GB |
dc.subject | neonatal diabetes | en_GB |
dc.subject | pancreas agenesis/hypoplasia | en_GB |
dc.subject | cholestasis | en_GB |
dc.title | Clinical characteristics and long-term follow-up of patients with diabetes due to PTF1A enhancer mutations | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-09-02T12:09:13Z | |
dc.identifier.issn | 0021-972X | |
dc.description | This is the final version. Available on open access from via the DOI in this record | en_GB |
dc.identifier.journal | Journal of Clinical Endocrinology and Metabolism | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-08-26 | |
exeter.funder | ::Diabetes UK | en_GB |
exeter.funder | ::Wellcome Trust | en_GB |
exeter.funder | ::Wellcome Trust | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-08-26 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-08-27T16:01:54Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-10-02T10:00:08Z | |
refterms.panel | A | en_GB |
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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.