Fig. 3

Main features of the AARS variant identified in the studied HDLS-S family. a Sanger sequence electropherograms showing the wild-type nucleotides present in an unaffected family member (on top) and the heterozygous variant found in both patients (bottom). b Multiple-species amino acid sequence alignment of AARS showing the variant region. Position 152, where the variant occurs, is marked with a red box. Species with reviewed sequences in the Uniprot database were selected for the alignment (P49588–1, Q8BGQ7–1, P50475–1, Q5RC02–1, Q8CFX8–1, O01541–1). The alignment was performed using Clustal Omega (https://www.ebi.ac.uk/Tools/msa/clustalo/). An ‘*’ (asterisk) on the bottom of the alignment indicates positions which have a single, fully conserved residue; a ‘:’ (colon) indicates conservation between groups of strongly similar properties; and a ‘.’ (period) indicates conservation between groups of weakly similar properties. c Comparison of the side chain of the wild-type Cysteine, a polar amino acid with a non-charged residue (green), and the larger aromatic side chain of the mutant, hydrophobic Phenylalanine (red). The image was obtained from the PDB structure 4XEM using the HOPE tool (http://www.cmbi.ru.nl/hope/about/). d Sanger sequence electropherograms after cDNA synthesis showing no splicing changes and similar expression of both alleles in occipital brain tissue of case 1 (bottom)