Identification of a Novel De Novo Variant in the PAX3 Gene in Waardenburg Syndrome by Diagnostic Exome Sequencing: The First Molecular Diagnosis in Korea.
Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including PAX3, MITF, SNAI2, EDNRB, EDN3, and SOX10, and many additional genes have been associated with disorders with phenotypic overlap with WS. To screen all possible genes associated with WS and congenital deafness simultaneously, we performed diagnostic exome sequencing (DES) in a male patient with clinical features consistent with WS. Using DES, we identified a novel missense variant (c.220C>G; p.Arg74Gly) in exon 2 of the PAX3 gene in the patient. Further analysis by Sanger sequencing of the patient and his parents revealed a de novo occurrence of the variant. Our findings show that DES can be a useful tool for the identification of pathogenic gene variants in WS patients and for differentiation between WS and similar disorders. To the best of our knowledge, this is the first report of genetically confirmed WS in Korea.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Mi-Ae
MA
Jang
Green Cross Genome, Yongin, Korea.
Taeheon
T
Lee
Green Cross Genome, Yongin, Korea.
Junnam
J
Lee
Green Cross Genome, Yongin, Korea.
Eun-Hae
EH
Cho
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chang-Seok
CS
Ki
D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005091:Exons; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D000072041:PAX3 Transcription Factor / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D014849:Waardenburg Syndrome / Q000175:diagnosis* / Q000235:genetics
D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D004247:DNA
Exome; PAX3; Waardenburg syndrome