Renal tubulopathies

Gene: HNF1B

Green List (high evidence)

Comment on list classification: Changing rating from red to green as many cases reported in OMIM associated with Renal cysts and diabetes syndrome.

Created: 5 Sep 2019, 3:37 p.m. | Last Modified: 5 Sep 2019, 3:37 p.m.

Panel Version: 1.126

Associated with Renal cysts and diabetes syndrome #137920 in OMIM.

Many cases reported in OMIM of cases with variants in HNF1B and Renal cysts and diabetes syndrome.

Also PMID: 19389850 - Adalat et al 2009- report an index case of a 13 year old boy with renal malformation who presented with tetany and hypomagnesemia. He was found to have a heterozygous HNF1B deletion as did his sister and father who also were found to have cystic kidneys. The sister and brother had hypocalciuria, while the father had hypomagnesemia. Of 91 futher patients with renal malformations in which HNF1B was screened, 21 (23%) had a heterozygous HNF1B mutation. 12 cases had a heterozygous HNF1B deletion c.1_1674del; p.Met1_Trp557del from 10 different families. 9 patients from 8 different families had heterozygous mutations detected by direct sequencing; 3 cases had frame shift mutations, 5 cases from 4 families had splice-site mutations and 1 with a missense mutation. 44% (eight of 18) mut+ patients had hypomagnesemia versus 2% (one of 48) mut− patients.

Created: 30 Aug 2019, 4:27 p.m. | Last Modified: 5 Sep 2019, 3:35 p.m.

Panel Version: 1.123

This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: HNF1B; Suggested initial gene rating: green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided

Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Renal cysts and diabetes syndrome, MIM 137920; Diabetes mellitus, noninsulin-dependent, MIM 125853

Variants in this GENE are reported as part of current diagnostic practice