DEMO Diabetes neonatal onset

Gene: HNF1B

Green List (high evidence)

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.

Green List (high evidence)

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.

Green List (high evidence)

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