Renal tubulopathies
Gene: EHHADHComment on list classification: Single family reported with additional functional data. Gene demoted to amber pending further evidence for re-evaluation.Created: 27 Mar 2019, 12:42 p.m.
Comment on list classification: 1 family plus functional data which is sufficient evidence to leave amber.Created: 4 Sep 2019, 3:37 p.m. | Last Modified: 4 Sep 2019, 3:37 p.m.
Panel Version: 1.84
PMID: 24401050 (Klootwijk et al 2014) - five-generation black family with isolated autosomal dominant Fanconi's syndrome. They found a heterozygous missense (p.E3K) mutation in EHHADH segregated with the disease. It results in a new mitochondrial targeting motif in the N-terminal portion of EHHADH. Functional studies of proximal tubular cells revealed impaired mitochondrial oxidative phosphorylation and defects in the transport of fluids and a glucose analogue across the epithelium. Further functional studies on the variant in PMID: 27160910 (Assmann et al 2016)
No other reports listed in OMIMCreated: 12 Feb 2019, 4:55 p.m.
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: EHHADH; Suggested initial gene rating: red; Evidence for inclusion: Klootwijk et al New Eng. J. Med. 370: 129-138, 2014. PubMed: 24401050, 1 large family, functional work; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none providedCreated: 3 Feb 2019, 11:32 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Fanconi renotubular syndrome 3 MIM 605615
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: Known expert and OMIM evidenceCreated: 10 May 2016, 10:52 a.m.
Mechanism involves mistargeting of mutant protein within cellCreated: 1 Nov 2015, 7:03 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria
Mode of pathogenicity
Other
Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615 to ?Fanconi renotubular syndrome 3, OMIM:615605; L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine
Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria to metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615
Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Publications for gene: EHHADH were set to 24401050
Publications for gene: EHHADH were set to
Source NHS GMS was added to EHHADH. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
Phenotypes for EHHADH were set to metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria
Mode of pathogenicity for EHHADH was changed to Other - please provide details in the comments
Mode of inheritance for EHHADH was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for EHHADH was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Green List (High Evidence).
EHHADH was added to Renal tubular acidosispanel. Sources: Expert