Monogenic hearing loss
Gene: HARS2
multiple independent families with Perrault syndrome reportedCreated: 31 Aug 2021, 1:21 p.m. | Last Modified: 31 Aug 2021, 1:21 p.m.
Panel Version: 2.180
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
sensorineural hearing loss; primary ovarian insufficiency
Publications
Several recent papers strengthening gene-disease association.Created: 2 Jan 2020, 4:39 a.m. | Last Modified: 2 Jan 2020, 4:39 a.m.
Panel Version: 2.4
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Perrault syndrome; deafness, autosomal recessive
Publications
Variants in this GENE are reported as part of current diagnostic practice
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 1:19 p.m. | Last Modified: 3 Mar 2022, 1:19 p.m.
Panel Version: 2.221
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major reviewCreated: 29 Jun 2020, 12:38 p.m. | Last Modified: 29 Jun 2020, 12:38 p.m.
Panel Version: 2.23
6 new cases, so now 8 independent cases, which is sufficient to rate green.
New cases:
PMID: 31827252 - Demain et al 2019 - 3 unrelated families each with compound heterozygous variants in HARS2 in affected members. All 3 families share the c.1439G>A p.(Arg480His) (NM_012208.3) variant along with other likely pathogenic variants.
PMID: 31449985 - Karstensen et al 2019 - three novel families, compound heterozygous for missense variants in HARS2 and early onset, rapidly progressive hearing impairment in the five affected individuals. Premature ovarian insufficiency was also seen in some individuals.Created: 28 Jan 2020, 11:56 a.m. | Last Modified: 28 Jan 2020, 11:56 a.m.
Panel Version: 2.4
Comment on list classification: Promoting from red to amber as there are now 2 independent cases of variants in HARS2 in patients with Perrault syndrome.Created: 26 Feb 2019, 4:01 p.m.
Associated provisionally with ?Perrault syndrome 2 (614926) in OMIM.
PMID: 21464306 - Pierce et al 2011 - nonconsanguineous family of mixed European ancestry with 5 affected siblings (3 females, 2 males) with Perrault syndrome. All had sensorineural hearing loss. The females also had ovarian dysgenesis. Affected individuals are compound heterozygous for HARS2 c.598C > G (p.L200V), and HARS2 c.1102G > T (p.V368L). As OMIM state functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.
PMID: 27650058 Lerat et al 2016 - Two unrelated Perrault syndrome patients from consanguineous families in Morocco had the same homozygous HARS2 mutation (c.1010A>G, p.Tyr337Cys). They presented with a similar phenotype: prelingual severe or profound deafness,secondary amenorrhea during the third decade, and no neurological sign. The originated from the same region in Morocco suggesting a founder effect.Created: 26 Feb 2019, 3:59 p.m.
Perrault syndrome, 3 DM mutations HGMD 2 families. Pierce et al 2011 family with 5 affected sibs all compound het, males have SNHL, females have ovarian dysgenesis and SNHL. Lerat et al 2016 PMID 27650058, affected patient homozygousCreated: 17 Feb 2019, 4:35 p.m.
Publications
Comment on list classification: Demoted from green to red.Created: 17 Feb 2016, 3:56 p.m.
Comment on list classification: Does not fit the guideline criteria for evidence.Created: 17 Feb 2016, 3:54 p.m.
1 family reported but good functional evidenceCreated: 13 Oct 2015, 8:40 p.m.
Tag for-review was removed from gene: HARS2.
Source Expert Review Green was added to HARS2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: HARS2 were changed from #614926:?Perrault syndrome 2 to Perrault syndrome 2, OMIM:614926
Publications for gene: HARS2 were set to 12056811; 15779907; 21464306; 517579; 7755634; 27650058
Tag for-review tag was added to gene: HARS2.
Gene: hars2 has been classified as Amber List (Moderate Evidence).
Publications for gene: HARS2 were set to PMID:12056811; 15779907; 21464306; 517579; 7755634
Gene: hars2 has been classified as Amber List (Moderate Evidence).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Phenotypes for HARS2 were set to #614926:?Perrault syndrome 2
Mode of inheritance for HARS2 was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Amber List (Moderate Evidence).
Publications for HARS2 were set to PMID:12056811; 15779907; 21464306; 517579; 7755634
HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert