DEMO Diabetes neonatal onset
Gene: GCK
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: GCK; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Fasting hyperglycaemia, permanent neonatal diabetes.Created: 11 Jan 2019, 4:27 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment when marking as ready: Marked as Ready: 25th May 2017.Created: 25 May 2017, 10:17 a.m.
Comment on list classification: Kept rating as Green: 2 cases (Norweigan and Italian) of permanent neonatal diabetes (MIM:606176) plus multiple cases of neonatal hypoglycemia. Rated green by expert reviewer, and part of Exeter neonatal diabetes screen.Created: 25 May 2017, 10:17 a.m.
Comment on mode of inheritance: Heterozygous GCK mutations cause MODY, and homozygous mutations cause neonatal diabetes. Based on advice from Elisa De-Franco (University of Exeter Medical School), I have changed the mode-of-inheritance from biallelic to both biallelic and monoallelic: in patients with heterozygous GCK mutations the fasting hyperglycemia is present from birth. So it is possible that (rarely) a patient is incidentally found to have high blood sugars in the neonatal period and thought to have neonatal diabetes, but they actually have GCK MODY.Created: 25 May 2017, 10:15 a.m.
Comment on mode of inheritance: Heterozygous GCK mutations cause MODY, and homozygous mutations cause neonatal diabetes. Based on advice from Elisa De-Franco (University of Exeter Medical School), I have changed the mode-of-inheritance from biallelic to both biallelic and monoallelic: in patients with heterozygous GCK mutations the fasting hyperglycemia is present from birth. So it is possible that (rarely) a patient is incidentally found to have high blood sugars in the neonatal period and thought to have neonatal diabetes, but they actually have GCK MODY.Created: 25 May 2017, 10:15 a.m.
From Illumina information for this gene, Pemanent neonatal diabetes mellitus and Transient neonatal diabetes have a recessive mode of inheritance, whereas Maturity Onset Diabetes of the Young has a dominant mode of inheritance.Created: 9 Sep 2015, 8:54 a.m.
Monoallelic - lifelong stable fasting hyperglycaemia
Biallelic - permanent neonatal diabetesCreated: 6 Jul 2015, 7:34 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mode of pathogenicity
loss-of-function (truncating variants and curated list of variants)
gene: GCK was added gene: GCK was added to DEMO Diabetes - neonatal onset. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Eligibility statement prior genetic testing,Expert Review Green,NHS GMS,UKGTN Mode of inheritance for gene: GCK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: GCK were set to Permanent neonatal diabetes; MODY, type II, 125851; Permanent Neonatal Diabetes Mellitus; Transient Neonatal Diabetes, Recessive; Diabetes mellitus, permanent neonatal, 606176; Diabetes mellitus, noninsulin-dependent, late onset, 125853; Fasting hyperglycaemia, permanent neonatal diabetes; Hyperinsulinemic hypoglycemia, familial, 3, 602485; Diabetes mellitus, gestational, 125851