2.4.2 Patient B
As a consequence of WES, a homozygous three-nucleotide deletion in exon 5 of FA2H was identified. The c.685_687delATC mutation was a non-frameshift deletion of nucleotides 685 to 687 (NM_024306) which leads to deletion of a non-polar, uncharged amino acid Isoleucine at 229th residue. For understanding the pattern of the inheritance, the proband’s relatives underwent co-segregation analysis. The results revealed heterozygotes status of parents and male fetus, suggesting an AR pattern of inheritance (shown in Figure 2). Since the pathogenicity of the mutation has not been reported in gene variant public databases, we applied several variant effect predictor websites to identify its potential pathogenicity. The predictors predicted the mutation according to ACMG parameters as a probably pathogenic variant (http://www.varsome.com/). Our analysis also showed that the nucleotides and their corresponding amino acid are highly conserved among different species (up to Chrysochloris Asiatica and considering 4 species) (shown in Figure 2).