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Identification of a Novel De Novo Variant in the PAX3 Gene in Waardenburg Syndrome by Diagnostic Exome Sequencing: The First Molecular Diagnosis in Korea.

Jang MA, Lee T, Lee J, Cho EH, Ki CS - Ann Lab Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Validation of a novel PAX3 variant by Sanger sequencing. The patient had a nonsynonymous substitution (c.220C>G; p.Arg74Gly, arrow) in PAX3. The patient's father and mother did not have this variant.
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Figure 2: Validation of a novel PAX3 variant by Sanger sequencing. The patient had a nonsynonymous substitution (c.220C>G; p.Arg74Gly, arrow) in PAX3. The patient's father and mother did not have this variant.

Mentions: The PAX3 variant was validated by Sanger sequencing in the patient and his parents. We confirmed the heterozygous PAX3 variant (NM_181457.3:c.220C>G, p.Arg74Gly) was present in the patient; however, his parents did not have the variant, indicating that it occurred de novo (Fig. 2).


Identification of a Novel De Novo Variant in the PAX3 Gene in Waardenburg Syndrome by Diagnostic Exome Sequencing: The First Molecular Diagnosis in Korea.

Jang MA, Lee T, Lee J, Cho EH, Ki CS - Ann Lab Med (2015)

Validation of a novel PAX3 variant by Sanger sequencing. The patient had a nonsynonymous substitution (c.220C>G; p.Arg74Gly, arrow) in PAX3. The patient's father and mother did not have this variant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390707&req=5

Figure 2: Validation of a novel PAX3 variant by Sanger sequencing. The patient had a nonsynonymous substitution (c.220C>G; p.Arg74Gly, arrow) in PAX3. The patient's father and mother did not have this variant.
Mentions: The PAX3 variant was validated by Sanger sequencing in the patient and his parents. We confirmed the heterozygous PAX3 variant (NM_181457.3:c.220C>G, p.Arg74Gly) was present in the patient; however, his parents did not have the variant, indicating that it occurred de novo (Fig. 2).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus