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Case Reports
. 2019 Jul;7(7):e00798.
doi: 10.1002/mgg3.798. Epub 2019 Jun 12.

A novel mutation of the PAX3 gene in a Chinese family with Waardenburg syndrome type I

Jing Ma  1 , Ken Lin  1 , Hong-Chao Jiang  2 , Yanli Yang  3 , Yu Zhang  2 , Guilian Yang  4 , Hao Sun  5 , Cheng Ming  1 , Xianyun Bi  1 , Tiesong Zhang  1 , Biao Ruan  3
Affiliations
Case Reports

A novel mutation of the PAX3 gene in a Chinese family with Waardenburg syndrome type I

Jing Ma et al. Mol Genet Genomic Med. 2019 Jul.

Abstract

Background: To analyze the clinical phenotypes and genetic variants of a Chinese family with Waardenburg syndrome (WS) and to explore the possible molecular pathogenesis of WS.

Methods: The clinical data from a patient and his family were collected. The genomic DNA of the patient and his family was purified from their peripheral blood. All exons and flanking sequences of the MITF, PAX3, SOX10, SNAI2, END3, and EDNRB genes were investigated through high-throughput sequencing. Based on the results of high-throughput sequencing, genetic variants in the patient and his family were verified and analyzed by Sanger sequencing.

Results: The patient was diagnosed with typical WS1 that manifested in hearing impairment, inner canthus ectopia and heterochromic iris. Sanger sequencing revealed the pathogenic heterozygous c.420-424de1CGCGGinsTTAC mutation in the PAX3 gene in the proband, which is a frameshift mutation that changed the amino acid sequence of the PAX3 protein from AVCDRNTVPSV to YSVIETPCRQ* (* refers to a stop codon) from amino acids 141-151. The stop codon induced by this mutation resulted in the truncation of the PAX3 protein. The same mutation sites were also found in the mother and younger sister of the proband. No previous report of this mutation was found in the Human Gene Mutation Database.

Conclusion: The novel heterozygous c.420-424de1CGCGGinsTTAC mutation is the molecular pathological cause for WS1 in our patient. The clinical and genetic characterization of this family with WS1 elucidated the genetic heterogeneity of PAX3 in WS1. Moreover, the mutation detected in this case has expanded the database of PAX3 mutations.

Keywords: PAX3; Waardenburg syndrome type I; gene mutation; hereditary deafness.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Clinical features and Family pedigree of the proband. Clinical features of the proband included iris heterochromia in both eyes (a); Clinical features of the proband's mother included iris heterochromia in both eyes (b); Clinical features of the proband's younger sister included iris heterochromia in the right eye (c); Family pedigree of the proband (d)
Figure 2
Figure 2
Clinical audiological examination. ASSR confirmed profound bilateral congenital sensorineural hearing loss (a); ABR confirmed profound bilateral congenital sensorineural hearing loss (b); Air conduction hearing threshold of the mother. Right ear, 50 dB HL; left ear, 70 dB HL. dB HL, decibel hearing level (c). ABR, auditory brain stem response; ASSR, auditory steady‐state responses
Figure 3
Figure 3
PAX3(NM_181457 0.3) sequencing map for the family with WS. The red arrow indicates the site of the base deletion
Figure 4
Figure 4
Amino acid coding diagram for the WS family. The red Ter indicates the site of the stop codon. The mutant caused the early termination of the coding sequence
See this image and copyright information in PMC

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