20 research outputs found
Annexes
I – Projet de journées d’études sur : modernisation et nouvelles formes de mobilisation sociale (EGYPTE ET BRESIL, 1970 – 1989) 1964 – 1967. Moments où s’essoufflent les régimes dits populistes, nationaux populaires, distributeurs, développementistes, au Brésil et en Égypte. Incapables de poursuivre plus loin le développement, c’est-à -dire d’assurer l’accumulation et le contrôle des ressources d’une part, et de laisser ouverts les canaux de la participation sociale et politique d’autre part, ..
Acid-catalyzed transfer sulfonation of anisole using overcrowded polymethylbenzenesulfonic acids
Modernisation et nouvelles formes de mobilisation sociale. Volume I : Égypte-Brésil (1970-1989)
Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations.
Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations
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 characterized.
Objective: To evaluate phenotype and genotype characteristics and long-term follow-up of patients with PTF1A enhancer mutations.
Setting: Twelve tertiary pediatric endocrine referral centers.
Patients: Thirty 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 hemoglobin) characteristics, pancreas imaging, and 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), anemia (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 extrapancreatic features which likely reflect long-term intestinal malabsorption.This article is available to RD&E staff via NHS OpenAthens (subject to any publisher embargo). Click on the Publisher URL, and log in with NHS OpenAthens if prompted.Genetic testing for neonatal diabetes was funded through a Wellcome Trust Senior Investigator award
(grant number: 098395/Z/12/Z). EDF is a Diabetes UK RD Law rence Fellow (19/005971), and SEF has a Sir Henry Dale Fellow ship jointly funded by the Wellcome Trust and the Royal Society (105636/Z/14/Z).published version, accepted version (12 month embargo), submitted versio