Primary Ovarian Insufficiency_Premature Ovarian Failure

Gene: HARS2

Green List (high evidence)

HARS2 (histidyl-tRNA synthetase 2, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000112855
EnsemblGeneIds (GRCh37): ENSG00000112855
OMIM: 600783, Gene2Phenotype
HARS2 is in 11 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Eight unrelated families reported to date, summarised in PMID 31827252. Clinical features include deafness and premature ovarian failure, no neurological abnormalities reported.
Created: 12 Sep 2020, 4:08 a.m. | Last Modified: 12 Sep 2020, 4:08 a.m.
Panel Version: 0.4377

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Perrault syndrome 2, MIM# 614926

Publications

Lauren Akesson (Royal Melbourne Hospital)

Green List (high evidence)

HARS2
There is sufficient evidence for a gene disease association between HARS2 and Perrault syndrome, with primary or secondary amenorrhoea, and hearing loss.

PMID: 31827252: compound heterozygous variants in HARS2 detected in 4 probands from 3 unrelated families. Three of the probands were male and one proband was a pre-pubertal female. Their phenotype was hearing loss.

PMID: 31486067: confirmed compound heterozygous variants in HARS2 were detected in in a proband with deafness, no information was provided as to the sex or age of the patient and whether there were features of Perrault syndrome.

PMID: 31449985: confirmed compound heterozygous variants in HARS2 were detected in 5 probands from 3 unrelated families with hearing impairment.
- The first family consisted of 2 pubertal females and 1 male. The females showed normal hormone measurements and normal ultrasound of internal reproductive organs
- The second family consisted of a pre-pubertal female with normal hormone measurements
- The third family consisted of a post-pubertal female with secondary amenorrhoea (never establishing regular menses). Perrault syndrome was diagnosed.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance.
Created: 3 Jul 2020, 1:55 a.m. | Last Modified: 3 Jul 2020, 1:55 a.m.
Panel Version: 0.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Perrault syndrome 2 (MIM# 614926)

Publications

Details

History Filter Activity

9 Jul 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: hars2 has been classified as Green List (High Evidence).

9 Jul 2020, Gel status: 3

Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

Phenotypes for gene: HARS2 were changed from ?Perrault syndrome 2 614926 to Perrault syndrome 2 614926

9 Jul 2020, Gel status: 3

Set publications

Bryony Thompson (Royal Melbourne Hospital)

Publications for gene: HARS2 were set to

24 Jun 2020, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: HARS2 was added gene: HARS2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HARS2 were set to ?Perrault syndrome 2 614926