DEMO Diabetes neonatal onset
Gene: HNF1B
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: HNF1B; 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: Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW.Created: 11 Jan 2019, 4:27 p.m.
We have 2 additional cases that have been identified by our lab.Created: 29 May 2017, 8:34 a.m.
Comment when marking as ready: Marked as Ready: 29th May 2017.Created: 29 May 2017, 8:36 a.m.
Comment on list classification: Updated rating from Red to Green: 2 published cases supporting gene:disease association (Yorifuji and Edghill), and 2 further cases reported by Dr Elisa De Franco as part of Exeter neonatal diabetes screen.Created: 29 May 2017, 8:36 a.m.
PMID:15181075 (Yorifuji et al, 2004) describe a missense mutation in HNF1B (C443G, S148W) in two siblings: one with neonatal diabetes mellitus and one with neonatal polycystic, dysplastic kidneys (with transient hyperglycemia which resolved spontaneously). This is the first report of permanent neonatal diabetes caused by a mutation of HNF1B.Created: 24 Apr 2017, 9:51 a.m.
Comment on mode of inheritance: Monoallelic mode of inheritance supported by literature.Created: 24 Apr 2017, 9:42 a.m.
PMID:17116179 (Edghill et al., 2006) identified a heterozygous S148L HNF1B mutation in one patient with neonatal diabetes diagnosed at 17 days.Created: 24 Apr 2017, 9:40 a.m.
Added 'mosaicism' tag based on PMID:15181075 (Yorifuji et al) which showed germline mosaicism of HNF1B; the unaffected mother was a low-level mosaic of normal and mutant HNF1B.Created: 24 Apr 2017, 9:24 a.m.
Comment on list classification: Promoted from amber to green due to two expert reviews.Created: 7 Jun 2016, 9:29 a.m.
Routine diagnostic testing for familial diabetes (usually with renal defects but should be included even without known renal disease due to variable expression).Created: 15 Oct 2015, 7:16 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
gene: HNF1B was added gene: HNF1B was added to DEMO Diabetes - neonatal onset. Sources: Expert Review Green,NHS GMS,Eligibility statement prior genetic testing,UKGTN Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNF1B were set to 17116179; 15181075; 26997508; 16207896; 15930087; 21993633 Phenotypes for gene: HNF1B were set to permanent neonatal diabetes mellitus; Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW; Diabetes mellitus, noninsulin-dependent, 125853; Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM)