Hereditary Neuropathy_CMT - isolated
Gene: YARS
More than 5 unrelated families reported.Created: 11 May 2021, 10:31 a.m. | Last Modified: 11 May 2021, 10:31 a.m.
Panel Version: 0.145
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323; MONDO:0012012
Publications
Seven affected children from a consanguineous family homozygous for a missense variant. Affected children expressed a more severe phenotype than previously reported, including 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. Carriers were asymptomatic (PMID: 30304524).
Homozygous missense variant in a patient with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease (PMID: 29232904)
Compound heterozygous variants identified in two siblings with failure to thrive (FTT), hypertriglyceridemia, developmental delay, liver dysfunction, lung cysts, and abnormal subcortical white matter (PMID: 27633801).
Note: loss of function is the mechanism of disease for the multisystem phenotypes mentioned in the above publications.
Dominant variants in YARS cause CMT in multiple patients. Functional studies performed in drosophila of 3 heterozygous missense variants recapitulate several features of human disease. Suspected gain of function disease mechanism (PMID: 19561293)Created: 20 Apr 2020, 3:15 a.m. | Last Modified: 20 Apr 2020, 3:15 a.m.
Panel Version: 0.2364
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
peripheral neuropathy; multisystem disease; CMT
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Gene: yars has been classified as Green List (High Evidence).
Phenotypes for gene: YARS were changed from Charcot Marie Tooth disease, dominant intermediate C, 608323; HMSN to Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323; MONDO:0012012
Publications for gene: YARS were set to
Mode of inheritance for gene: YARS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
gene: YARS was added gene: YARS was added to Hereditary Neuropathy - isolated_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: YARS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: YARS were set to Charcot Marie Tooth disease, dominant intermediate C, 608323; HMSN