2.4.1 Patient A
In patient A, following WES, a frameshift variant defined as c.1568delC (NM_014844, 14:102434385 GCR38, p.S523Ffs*12) in exon 9 ofTECPR2 was identified. This variant was not found neither in GenomeAD, 1000genome, Iranome databases nor in our local database for 300 Lur individuals, being extremely rare. The c.1568delC variant was a single nucleotide deletion of cytosine, leading to a premature stop codon only 11 amino acids after deletion site (shown in Figure 1).TECPR2 encodes 1411 amino acid length protein in canonical isoform (NM_014844), which contains three WD and ten TECPR domains. As a consequence of this frameshift mutation, approximately 63% of critical region of original protein is eliminated after translation, remaining only 37%. In addition, another homozygous deletion defined as c.1135_1136del (NM_024101, 2:237540378 GRC38, p.D379Cfs*19) in exon 10 of MLPH was detected in the proband. This mutation describes the grisclli appearance of affected siblings, since mutations in this gene have been reported with Griscelli syndrome, type 3. Genotyping family members including mother and siblings reveled that affected sister harbored c.1568delC variant in homozygote manner, while mother and the healthy elder daughter of the family were carriers (shown in Figure 1). However, father of the family was unavailable to participate in the study. As expected, two affected siblings were homozygote for c.1135_1136 deletion in MLPH , confirming the Griscelli syndrome, type 3 in the family.