affected siblings on chromosome 3 (Fig. 6c). Confirmatory Sanger sequencing validated the full segregation of this variant with the disease in the family in a fully penetrant autosomal-recessive model, being homozygous in both patients and heterozygous in the parents and the healthy sibling (Fig. 6d). The genetic alteration is expected to cause a nonsense mutation due to the introduction of a UAA stop codon within the mRNA transcript encoding the predominant isoform of DALRD3 (pTyr417*). Translation of this transcript will result in a truncated protein lacking the DALR tRNA anticodon-binding domain. In addition, the variant DALRD3 mRNA could be subject to NMD due to the presence of a premature stop codon.
