[Application of next generation sequencing in 3 Waardenburg syndrome].

Objective

To test the gene sequence of 3 patients with Waardenburg syndrome（WS） using the next generation sequencing technology in order to explore the possible mechanism of molecular genetics.

Methods

Medical histories of the family members were collected. Physical examination, audiological evaluation and CT examination were performed. Peripheral blood was collected and DNA was extracted. The exon region of 159 deafness genes, 6 mitochondrial genes and 3 miRNAs of the proband were tested by next generation sequencing. The mutation sites of the possible pathogenic genes were obtained, subsequently, Sanger sequencing verification was performed on the proband and family members.

Results

The first proband had a heterozygous mutation in exon 7 of MITF gene（NM_000248）: c.641_643delGAA; The second proband had a heterozygous mutation in exon 10 of MITF gene（NM_001354605）: c.1177-1G>A; The third proband had a heterozygous mutation in exon 5 of PAX3 gene（NM_181457）: c.587_593delCCTCAGC; The parents of the three probands verified by Sanger sequencing that there was no variation at the corresponding sites, and the above mutations were spontaneous mutations.

Conclusion

Next generation sequencing can more comprehensively analyze information of the carried status and genetic rules of the disease-associated gene in WS families, and provide guidance for family reproductives.