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Case Reports
. 2017 Dec 11;8(12):381.
doi: 10.3390/genes8120381.

An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS

Anna Tracewska-Siemiątkowska  1   2 , Lonneke Haer-Wigman  3 , Danielle G M Bosch  4   5   6 , Deborah Nickerson  7 , Michael J Bamshad  8 ; University of Washington Center for Mendelian Genomics  9 ; Maartje van de Vorst  10   11 , Nanna Dahl Rendtorff  12 , Claes Möller  13 , Ulrika Kjellström  14 , Sten Andréasson  15 , Frans P M Cremers  16   17 , Lisbeth Tranebjærg  18   19
Affiliations
Case Reports

An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS

Anna Tracewska-Siemiątkowska et al. Genes (Basel). .

Abstract

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.

Keywords: YARS; syndromic retinitis pigmentosa; whole exome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient’s electroretinogram showing no residual rod responses and decreased, but still detectable cone responses in both eyes. ERG: electroretinography.
Figure 2
Figure 2
Pedigree and mutation data for the YARS gene. (A) binary SAM (BAM) file visualization in Integrative Genomics Viewer (IGV) software [11] displaying the variant site in the whole trio; (B) Familial segregation analysis with Sanger sequencing; (C) AlaMut Visual amino acid conservation in animal orthologs.
Figure 3
Figure 3
YARS domains and locations of autosomal dominant (AD) mutations causing CMT (black) and autosomal recessive (AR) mutations (grey—Nowaczyk et al.; red—this study).
See this image and copyright information in PMC

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