A Case Report Study of Shah-Waardenburg Syndrome in Consanguineous Family

Background and aim: ws, regarded as neurocristopathies, involves neural crest-derived cells in embryonic development. shah-waardenburg syndrome (ws type 4) is a rare mendelian disorder, described with numerous clinical expression, main clinical features are oculocutaneous anomalous, deafness, hirschsprung disease, poliosis above the forehead, and growth retardation. ws can be inherited in both autosomal dominant and recessive patterns. we aimed to study newborn type4 patients of consanguineous marriages family via high throughput methods. in this study, whole-exome sequencing was performed in order to identify the causal genes, mechanism, and kind of mutation occur in subtype ws4 patient. a family segregating in the pedigree was also determined in a genetic counseling center, so we investigate denovo mutation causing the clinical traits.methods: dna was isolated from peripheral blood by standard methods. whole-exome sequencing was performed using, illumina hiseq 4000. resulting fastq file quality were checked via fastqc software. files were mapped against the reference genome provided by gnomad and gnomex databases. output files were validated and sorted via excel softwareresults: results candidate variants that related with ws type 4. results will confirm by sanger sequencing and will be published soon. we hope our data can provide a new insight for this rare syndrome in iranian population.conclusion: in general, consanguineous marriage has shown significantly higher in many genetic abnormalities which suggest that couples may have harmful genes. ws rarity and genetic heterogeneity limited the ability to make accurate clinical diagnosis in individual patients. whole exome sequencing has been represented as a powerful approach to elucidate the genetic basis of rare hereditary disorders in familial cases. in most reported ws-4 cases, the sox10 gene has been identified as a candidate gene caused waardenburg type 4. mutations in the edn3, ednrb also reported in ws patients, due to the family segregating we'd expect de novo mutation.