Cholestasis

Gene: YARS

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 4:18 p.m. | Last Modified: 3 Mar 2022, 4:18 p.m.

Panel Version: 1.105

Green List (high evidence)

PMID 33490854 (2021) - Case report of homozygous biallelic variant inherited from heterozygous parents, child affected with complex clinical conditions culminating in death at 12 months of age. PMID 33490854 reports a case with failure to thrive and cholestatic hepatitis, followed by progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay, amongst other features. Autopsy confirmed significant end-stage fibrotic liver disease with cholestasis.
Sources: Literature

Created: 12 Feb 2022, 4:47 p.m. | Last Modified: 12 Feb 2022, 5:01 p.m.

Panel Version: 1.103

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
failure to thrive (FTT); cholestatic hepatitis; progressive liver disease; exocrine pancreatic insufficiency; acute renal failure; recurrent infections; ichthyosis; hematologic concern; , hypotonia; global developmental delay

Publications

• 33490854

I don't know

The new gene for YARS is YARS1

Created: 5 Aug 2020, 4:57 p.m. | Last Modified: 5 Aug 2020, 4:57 p.m.

Panel Version: 1.16

Comment on phenotypes: Monoallelic variants are associated with Charcot-Marie-Tooth disease, dominant intermediate C 608323, while biallelic variants are associated with a complex phenotype that may include intellectual disability, hearing loss and liver damage.

Created: 5 Aug 2020, 4:54 p.m. | Last Modified: 5 Aug 2020, 4:54 p.m.

Panel Version: 1.16

Biallelic variants in three families with complex clinical conditions including developmental delay and liver damage. PMID 30304524 reports an extended family with microcephaly, expressive language delay, hearing loss, cholestatic liver disease, amongst other features. PMID 29232904 reports a proband whose phenotype included hearing loss, retnititis pigmentosa, hypotonia, transiant fatty liver, but did not include intellectual disability. PMID 27633801 reports two sibblings with hypotionia and liver dysfunction. The older brother at 15 years of age has mild delays, he attends school on an individualized educational program and functions at a grade 3 level.
Sources: Literature

Created: 5 Aug 2020, 4:52 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease, dominant intermediate C 608323; Intellectual disability; deafness; nystagmus; liver dysfunction

Publications

• 30304524
• 29232904
• 27633801