Subject(s)
Bulbar Palsy, Progressive/drug therapy , Bulbar Palsy, Progressive/physiopathology , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sensorineural/physiopathology , Receptors, G-Protein-Coupled/deficiency , Riboflavin/pharmacokinetics , Vitamin B Complex/pharmacokinetics , Adult , Bulbar Palsy, Progressive/genetics , Hearing Loss, Sensorineural/genetics , Humans , Male , Riboflavin/administration & dosage , Vitamin B Complex/administration & dosageABSTRACT
Whole exome sequence analysis was performed in a Swedish mother-father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A homozygous variant c.806T > C, p.(F269S) in the tyrosyl-tRNA synthetase gene (YARS) was the only identified candidate variant consistent with autosomal recessive inheritance. Mutations in YARS have previously been associated with both autosomal dominant Charcot-Marie-Tooth syndrome and a recently reported autosomal recessive multiorgan disease. Herein, we propose that mutations in YARS underlie another clinical phenotype adding a second variant of the disease, including retinitis pigmentosa and deafness, to the spectrum of YARS-associated disorders.