Identification of a de novo, Novel Pathogenic Variant in the Splice Region of the Gene in an Iranian Azeri Turkish Family with Waardenburg Syndrome.

BACKGROUND

Waardenburg syndrome (WS) is an inherited heterogeneous auditory pigmentary syndrome, divided into at least four types and characterized by iris heterochromia, white forelock, prominent nasal root, dystopia canthorum, middle eyebrow hypertrichosis, and deafness. Pathogenic variants in the gene have been reported to be involved in WS disease.

METHODS

Whole exome sequencing (WES) was conducted on a 24-year-old male, who originated from Iranian Azeri Turkish ethnic group, with symptoms of deafness and blue eyes from brown-eyed parents. Web-based tools including Mutation Taster, VarSome, SIFT, Human Splicing Finder (HSF), and I-TASSER, were used for bioinformatics analysis. To verify the WES findings, DNAs taken from the blood samples of all family members were subjected to PCR-Sanger sequencing.

RESULTS

A novel heterozygous pathogenic variant, NC_000022.11 (NM_006941):c.428+1G>T, located in the second intron of the gene and disrupting the splicing site, was identified in the proband. Sanger sequencing was applied on the proband and his parents. The results showed that the variant was a de novo pathogenic variant with an autosomal dominant inheritance pattern.

CONCLUSIONS

Identification of a novel de novo pathogenic variant, NC_000022.11 (NM_006941):c.428+1G>T, in the second intron of the gene with autosomal dominant inheritance pattern.