Hereditary Neuropathy - complex
Gene: KARS
Only reported in one individual however functional analysis shows variants in KARS could be important for a diagnosis of CMT.
PMID: 20920668
Genes encoding aminoacyl-tRNA synthetases (ARS) are known to be causative of Charcot Marie Tooth.
Reported one individual with an intermediate CMT phenotype with peripheral neuropathy.
The individual was a compound heterozygote (p.Leu133His; p.Tyr173SerfsX7).
Structural functional analysis on the ARAS enzyme showed the frameshift mutation is predicted to result in a complete loss of function of the catalytic domain.
In vitro functional assay using human cytoplasmic tRNA was synthesised. The functional assay showed the p.Leu133His variant severely impairs enzyme activity resulting in >90% of the catalytic efficiency.Created: 13 Jul 2023, 11:40 p.m. | Last Modified: 13 Jul 2023, 11:40 p.m.
Panel Version: 0.169
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641; MONDO:0013338)
Publications
Gene: kars has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: KARS were changed from HMSN; Charcot Marie Tooth disease, recessive intermediate, B, 613641; Deafness, autosomal recessive 89, 613916 to Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641; MONDO:0013338)
Publications for gene: KARS were set to
Gene: kars has been classified as Amber List (Moderate Evidence).
gene: KARS was added gene: KARS was added to Hereditary Neuropathy - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: KARS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KARS were set to HMSN; Charcot Marie Tooth disease, recessive intermediate, B, 613641; Deafness, autosomal recessive 89, 613916