Case Report: Identification of an HNF1B p.Arg527Gln mutation in a Maltese patient with atypical early onset diabetes and diabetic nephropathy

BMC Endocrine Disorders
Nikolai Paul PaceJosanne Vassallo

Abstract

The diagnosis of atypical non-autoimmune forms of diabetes mellitus, such as maturity onset diabetes of the young (MODY) presents several challenges, in view of the extensive clinical and genetic heterogeneity of the disease. In this report we describe a case of atypical non autoimmune diabetes associated with a damaging HNF1β mutation. This is distinguished by a number of uncharacteristic clinical features, including early-onset obesity, the absence of renal cysts and diabetic nephropathy. HNF1β-MODY (MODY5) is an uncommon form of monogenic diabetes that is often complicated by a wide array of congenital morphological anomalies of the urinary tract, including renal cysts. This report expands on the clinical phenotypes that have been described in the context of HNF1β mutations, and is relevant as only isolated cases of diabetic nephropathy in the setting of MODY5 have been reported. An obese Maltese female with non-autoimmune diabetes, microalbuminuria, glomerular hyperfiltration, fatty liver and no renal cysts was studied by whole exome sequencing to investigate potential genes responsible for the proband's phenotype. A rare missense mutation at a highly conserved site in exon 8 of HNF1β was identified (c.1580G > A, NM_000458....Continue Reading

References

Oct 7, 2000·European Journal of Endocrinology·A F ReisG Velho
Apr 8, 2004·Annals of Internal Medicine·Christine Bellanné-ChantelotJosé Timsit
Oct 22, 2004·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Coralie Bingham, Andrew T Hattersley
Oct 29, 2004·Human Molecular Genetics·Elena BarbacciSilvia Cereghini
Sep 15, 2006·Journal of the American Society of Nephrology : JASN·Stefanie WeberRemi Salomon
Dec 26, 2006·Molecular Genetics and Metabolism·Rosienne FarrugiaAlex E Felice
May 7, 2009·The Journal of Clinical Endocrinology and Metabolism·Klemens RaileAnnette Grüters
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jul 16, 2009·Genome Research·Sung Chun, Justin C Fay
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Apr 10, 2010·Clinical Journal of the American Society of Nephrology : CJASN·Laurence HeidetRémi Salomon
May 17, 2012·Diabetic Medicine : a Journal of the British Diabetic Association·E L EdghillS Ellard
Jun 19, 2013·The Journal of Clinical Endocrinology and Metabolism·Catherine PihokerUNKNOWN SEARCH for Diabetes in Youth Study Group
Jan 11, 2014·Diabetes Technology & Therapeutics·Sekar KanthimathiVenkatesan Radha
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow
Sep 4, 2014·Pediatric Diabetes·Oscar Rubio-CabezasUNKNOWN International Society for Pediatric and Adolescent Diabetes
Dec 17, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anke RaaijmakersElena Levtchenko
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Jul 15, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Detlef Bockenhauer, Graciana Jaureguiberry
Apr 20, 2017·Diabetes Care·Danièle Dubois-LaforgueUNKNOWN Monogenic Diabetes Study Group of the Société Francophone du Diabète

❮ Previous
Next ❯

Citations

May 16, 2020·International Journal of Endocrinology·Juyi LiAiping Deng
Dec 14, 2018·Journal of Cellular Biochemistry·Filipa Lopes-CoelhoJacinta Serpa

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
electrophoresis
PCR
biopsies

Software Mentioned

MutationTaster
PolyPhen
SAMTools
Illumina RTA
FATHMM
DANN
MetaSVN
Polyphen2
MelaLR
gnomAD

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.