Renal tubulopathies

Gene: CLCNKA

Comment on list classification: The rating of this gene is being changed to Red from Amber, to reflect that GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.

Created: 10 Aug 2023, 12:32 p.m. | Last Modified: 10 Aug 2023, 12:32 p.m.

Panel Version: 4.9

Comment on mode of inheritance: Digenic CLCNKA & CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090)(PMID: 15044642;18310267;32488762). The current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.

Created: 10 Aug 2023, 12:18 p.m. | Last Modified: 10 Aug 2023, 12:18 p.m.

Panel Version: 4.7

I don't know

Comment on list classification: 2 reported cases. But note disease association is digenic.

Created: 4 Sep 2019, 8:49 p.m. | Last Modified: 4 Sep 2019, 8:49 p.m.

Panel Version: 1.97

Comment on mode of inheritance: Digenic recessive with CLCNKB variants.

Created: 4 Sep 2019, 8:48 p.m. | Last Modified: 4 Sep 2019, 8:48 p.m.

Panel Version: 1.96

Associated with Bartter syndrome, type 4b, digenic (#613090) in OMIM.

PMID: 15044642 - Schlingmann et al 2004 - in a child with a child with renal salt wasting and deafness, they identified both a homozygous deletion of the CLCNKB gene and a homozygous trp80-to-cys mutation in the CLCNKA gene (W80C).

Nozu et al 2008 - 2-year-old Japanese girl with a severe form of Bartter syndrome with sensorineural deafness. Parents were nonconsanguineous. They found 2 heterozygous mutations in the CLCNKA and CLCNKB genes on the paternal allele, and a 12-kb deletion involving portions of the CLCNKA and CLCNKB genes on the maternal allele. Neither parent was clinically affected.

Created: 29 Aug 2019, 4:33 p.m. | Last Modified: 29 Aug 2019, 4:33 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: CLCNKA; Suggested initial gene rating: amber; Evidence for inclusion: Nozu et al J. Med. Genet. 45: 182-186, 2008. PubMed: 18310267. 2 patients reported with both 2 CLCNKB and 2 CLCNKA mutations, severe phenotype and hearing loss;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
Unknown

Phenotypes
Bartter syndrome, type 4b, digenic MIM 613090

Publications

• Nozu et al J. Med. Genet. 45: 182-186, 2008. PubMed: 18310267

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