PMID: 15220213Jun 29, 2004Paper

Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity

Diabetes
Valérie SenéeCécile Julier

Abstract

Wolcott-Rallison syndrome (WRS) is a rare autosomal-recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystemic clinical manifestations. Based on genetic studies of two inbred families, we previously identified the gene responsible for this disorder as EIF2AK3, the pancreatic eukaryotic initiation factor 2alpha (eIF2alpha) kinase. Here, we have studied 12 families with WRS, totalling 18 cases. With the exception of one case, all patients carried EIF2AK3 mutations resulting in truncated or missense versions of the protein. Exclusion of EIF2AK3 mutations in the one patient case was confirmed by both linkage and sequence data. The activities of missense versions of EIF2AK3 were characterized in vivo and in vitro and found to have a complete lack of activity in four mutant proteins and residual kinase activity in one. Remarkably, the onset of diabetes was relatively late (30 months) in the patient expressing the partially defective EIF2AK3 mutant and in the patient with no EIF2AK3 involvement (18 months) compared with other patients (<6 months). The patient with no EIF2AK3 involvement did...Continue Reading

References

Feb 1, 1972·The Journal of Pediatrics·C D Wolcott, M L Rallison
Mar 1, 1982·European Journal of Pediatrics·H StössJ Spranger
May 23, 1998·Journal of Medical Genetics·D T BonthronL I Al-Gazali
Oct 13, 2001·American Journal of Human Genetics·J NerupUNKNOWN European Consortium for IDDM Studies
Dec 1, 2001·Nature Genetics·C Julier
Mar 29, 2002·Nature Genetics·Scott D Briggs, Brian D Strahl
Jun 8, 2002·Nature Genetics·Augustine KongKari Stefansson
Sep 5, 2002·American Journal of Medical Genetics·Bassam Bin-AbbasAbdullah Al-Ashwal
Mar 20, 2003·Current Diabetes Reports·David Q Shih, Markus Stoffel

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Citations

May 6, 2011·Diabetologia·L RussoUNKNOWN ISPED Early Diabetes Study Group
Jul 11, 2007·Pediatric Radiology·Sandra L Wootton-Gorges, Nicole S Glaser
May 27, 2008·Journal of Inherited Metabolic Disease·O SøvikA Molven
Aug 16, 2008·Journal of Inherited Metabolic Disease·G EngelmannC R Buchanan
Jan 22, 2010·Indian Journal of Pediatrics·C M BatraVimal Gupta
Feb 28, 2008·Nature Clinical Practice. Endocrinology & Metabolism·Rinki MurphyAndrew T Hattersley
Sep 1, 2007·Antioxidants & Redox Signaling·Ronald C Wek, Douglas R Cavener
Jul 14, 2005·Current Opinion in Pediatrics·Mark A Sperling
Oct 17, 2012·Molecular and Cellular Biology·Yan GaoJ Alan Diehl
May 3, 2008·The Journal of Clinical Investigation·Carlo ColomboUNKNOWN Early Onset Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (SIEDP)
Nov 6, 2010·Orphanet Journal of Rare Diseases·Cécile Julier, Marc Nicolino
Apr 26, 2008·Endocrine Reviews·Lydia Aguilar-Bryan, Joseph Bryan
Oct 20, 2009·The Journal of Clinical Endocrinology and Metabolism·Oscar Rubio-CabezasSian Ellard
Jun 9, 2011·Journal of Pediatric Endocrinology & Metabolism : JPEM·Yanmei SangGuichen Ni
Jun 14, 2013·The Libyan Journal of Medicine·Abdelhadi M Habeb
May 16, 2012·Advances in Nutrition·Thomas D Baird, Ronald C Wek
Oct 19, 2013·Cellular and Molecular Life Sciences : CMLS·Joseph W Brewer
Sep 17, 2009·Apoptosis : an International Journal on Programmed Cell Death·Carla J H van der KallenCasper G Schalkwijk
Jul 18, 2014·Alzheimer's Research & Therapy·Tao Ma, Eric Klann
Aug 8, 2007·Nature Reviews. Genetics·Gert C ScheperChristopher G Proud
May 7, 2013·European Journal of Pediatrics·C P HawkesN P Murphy
Mar 14, 2007·Médecine sciences : M/S·Fabienne Foufelle, Pascal Ferré
Oct 4, 2015·Diabetic Medicine : a Journal of the British Diabetic Association·A UçarE Tunçez
Jul 16, 2005·Annals of Medicine·Annabelle S Slingerland, Andrew T Hattersley
May 8, 2007·FEBS Letters·Min Ni, Amy S Lee
Jan 29, 2013·Hematology/oncology Clinics of North America·Marshall S HorwitzTimothy Tidwell
Feb 12, 2014·Scientific Reports·Feyza EnginGökhan S Hotamisligil
Apr 29, 2005·Diabetes/metabolism Research and Reviews
Jun 6, 2009·Pediatric Diabetes·Daniela Seick BarbariniBurkhard Simma
Sep 17, 2009·Pediatric Diabetes·Andrew HattersleyKim C Donaghue
Jan 11, 2007·Pediatric Diabetes·Andrew HattersleyUNKNOWN International Society for Pediatric and Adolescent Diabetes
Apr 27, 2011·Pediatric Diabetes·André F ReisGilberto Velho

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