Monogenic hearing loss

Gene: YARS

Green List (high evidence)

Comment on phenotypes: OMIM phenotype updated 8th Oct 2026.

Created: 8 Oct 2026, 2:33 p.m. | Last Modified: 8 Oct 2026, 2:33 p.m.

Panel Version: 6.46

Comment on list classification: There are now at least 5 unrelated probands reported in literature with biallelic YARS (new name YARS1) variants and a multisystem disorder including hearing loss. Hence, this gene can be promoted to Green on Monogenic hearing loss.

Created: 8 Oct 2026, 2:27 p.m. | Last Modified: 8 Oct 2026, 2:27 p.m.

Panel Version: 6.45

PMID: 38125821 Kuan et al., 2023
Report of a Hispanic individual with dysmorphic facies and neurological issues. Admitted in the neonatal period due to seizure-like activity, vomiting, and poor feeding. Brain MRI yielded no significant findings. An abdominal ultrasound revealed an echogenic liver. He had hearing loss in his left ear. Subsequently diagnosed with microcephaly, hypotonia, nystagmus, and significant developmental delays. Laboratory tests indicated anemia.
A microarray conducted shortly after birth revealed 47, XXY. WES uncovered a paternally inherited YARS: c.1099C > T, p.Arg367Trp variant & a maternally inherited YARS: c.782T > G, p.Leu261Arg. Father has history of hearing loss and neurological symptoms; mother was unaffected.

PMID: 34536092 Averdunk et al., 2021
Study identified 12 individuals from 6 families with the recurrent homozygous missense variant c.1099C > T;p.(Arg367Trp) in YARS. Patients presented with a multisystem disorder with developmental delay (12/12), microcephaly (12/12), failure to thrive, short stature, muscular hypotonia (9/12), ataxia, brain anomalies, microcytic anemia (8/8 assessed), hepatomegaly (7/7 assessed), and hypothyroidism. Seq method: exome sequencing. Haplotype analysis showed that the haplotype of individuals originating from Saudi Arabia (C-I) differs from the haplotypes of individuals A + B (from Turkey) and L (from Puerto Rico) - supportive of a recurrent rather than a founder variant. 2 unrelated individuals had hearing loss.

PMID 30304524 Williams et al., 2019
Report of 7 related Amish children homozygous for YARS, c.499C>A, p.Pro167Thr (seq method: WES). Phenotype: poor growth, developmental delay, brain dysmyelination, sensorineural hearing loss, nystagmus, progressive cholestatic liver disease, pancreatic insufficiency, hypoglycemia, anemia, intermittent proteinuria, recurrent bloodstream infections and chronic pulmonary disease. Bilateral sensorineural hearing loss and cholestatic liver disease were present in 7/7 affected individuals. Related adult het carriers were asymptomatic.

PMID: 29232904 Tracewska-Siemiątkowska et al., 2017
Report of a Swedish proband homozygous for YARS: c.806T>C, p.(F269S). Method: Trio WES. Phenotype of the proband: progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. Het parents unaffected.

Created: 8 Oct 2026, 2:21 p.m. | Last Modified: 8 Oct 2026, 2:36 p.m.

Panel Version: 6.46

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, OMIM:619418; neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2, MONDO:0030375

Publications

• 29232904
• 30304524
• 34536092
• 38125821

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: 2.40

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, 4:55 p.m. | Last Modified: 5 Aug 2020, 4:55 p.m.

Panel Version: 2.39

Biallelic variants in three families with complex clinical conditions including developmental delay. PMID 30304524 reports an extended family with microcephaly, expressive language delay, hearing loss, amongst other features. PMID 29232904 reports a proband whose phenotype included hearing loss, retnititis pigmentosa and hypotonia, but did not include intellectual disability. PMID 27633801 reports two sibblings with hypotionia, 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, but not hearing loss was reported.
Sources: Literature

Created: 5 Aug 2020, 4:43 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