Renal tubulopathies

Gene: ATP1A1

Green List (high evidence)

Comment on list classification: Promoting red to green as there are 3 cases plus some functional data.

Created: 4 Sep 2019, 3:43 p.m. | Last Modified: 4 Sep 2019, 3:43 p.m.

Panel Version: 1.90

Associated with Hypomagnesemia, seizures, and mental retardation 2 (#618314) in OMIM.

PMID: 30388404 - Schlingmann et al 2018 - describe 3 unrelated infants who are from non-consanguineous families and who presented with a disease phenotype consisting of generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Whole-exome sequencing and conventional Sanger sequencing identified heterozygous de novo mutations in ATP1A1 (p.Leu302Arg, p.Gly303Arg, p.Met859Arg). Functional studies show the critical role of the α1 subunit of Na+, K+-ATPase for the maintenance of ionic gradients, the generation of resting membrane potential, and the termination of neuronal activity in the central nervous system

Created: 29 Aug 2019, 4:07 p.m. | Last Modified: 29 Aug 2019, 4:07 p.m.

Panel Version: 1.82

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: ATP1A1; Suggested initial gene rating: green; Evidence for inclusion: Schlingmann et al 2018 Am J Hum Genet 103 (5) 808-816. PMID: 30388404, 3 families, all de novo;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 hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, MIM 618036

Publications

• Schlingmann et al 2018 Am J Hum Genet 103 (5) 808-816. PMID: 30388404