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).