Likely inborn error of metabolism - targeted testing not possible
Gene: HARS2Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))Created: 19 Sep 2019, 3:22 p.m. | Last Modified: 19 Sep 2019, 3:22 p.m.
Panel Version: 1.302
Comment on publications: PMID: 21464306: One family reported, with five affected siblings who were compound heterozygous for variants L200V and V368L. Functional evidence in c.elegans was provided. PMID: 27650058: patients with sporadic Perrault syndrome IV-1 and VI-I were homozygous for the c.1010A>G (p.Tyr337Cys) variant. The patients were claimed not to be related, but originated from the same region in Morocco and the variant was characterised as being in the same haplotype, suggesting a founder effect. Found at a frequency of 1/121332 in Exac.Created: 19 Sep 2019, 3:20 p.m. | Last Modified: 19 Sep 2019, 3:20 p.m.
Panel Version: 1.301
Comment on list classification: This gene was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. It was confirmed that Perrault syndrome was relevant for this panel, and that there was enough evidence for the gene to be Green.Created: 19 Sep 2019, 3:19 p.m. | Last Modified: 19 Sep 2019, 3:19 p.m.
Panel Version: 1.300
Found a second publication, and also another couple P/LP variants reported in ClinVar. Probably merits Amber.Created: 30 Aug 2018, 4:22 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Perrault syndrome 2, MIM#614926
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on publications: PMID: 21464306: One family reported, with five affected siblings who were compound heterozygous for variants L200V and V368L. Functional evidence in c.elegans was provided. PMID: 27650058: patients with sporadic Perrault syndrome IV-1 and VI-I were homozygous for the c.1010A>G (p.Tyr337Cys) variant. The patients were claimed not to be related, but originated from the same region in Morocco and the variant was characterised as being in the same haplotype, suggesting a founder effect. Found at a frequency of 1/121332 in Exac.Created: 25 Feb 2019, 5:21 p.m.
Comment on list classification: This gene was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. It was confirmed that Perrault syndrome was relevant for this panel, and that there was enough evidence for the gene to be Green.Created: 25 Feb 2019, 5:19 p.m.
Comment when marking as ready: Reviewed for the congenital hearing panel, and there is currently not enough evidence to promote this gene from red to green.Created: 2 Mar 2016, 12:26 p.m.
Comment on mode of inheritance: Sourced from OMIM.Created: 2 Mar 2016, 12:26 p.m.
Source Expert Review Green was added to HARS2. Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 2, 614926 for gene: HARS2 Publications for gene HARS2 were changed from 27604308 to 27650058; 21464306 Rating Changed from Red List (low evidence) to Green List (high evidence)
Source NHS GMS was added to HARS2. Source London North GLH was added to HARS2.
Sarah Leigh: Associated with phenotype in O
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 2, 614926 for gene: HARS2
gene: HARS2 was added gene: HARS2 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HARS2 were set to 27604308 Phenotypes for gene: HARS2 were set to ?Perrault syndrome 2 614926; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))