June 14th, 2021

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Prenatal Diagnosis of Waardenburg Syndrome Type I in a Chinese Family
Authors:  Wei Ren, M.D., Weixin Cui, M.D., Chengcheng Zhang, M.D., Xu Liu, M.D., and Bo Wang, M.D.
  OBJECTIVE: To perform prenatal diagnosis for Waardenburg syndrome type I and to detail the clinical and genetic investigations used.

STUDY DESIGN: The clinical data from the proband and her family were collected. Genomic DNA was purified from peripheral blood cells. Exons and flanking sequences of PAX3, MITF, END3, SOX10, SNAI2, and EDNRB genes were analyzed by high‐throughput sequencing. Identified genetic variants were further verified by Sanger sequencing. For prenatal diagnosis, we performed cytogenetic analysis of the amniocytes, conventional karyotyping, and array comparative genomic hybridization (aCGH).

RESULTS: The proband was diagnosed as Waardenburg syndrome type I (WS1) with two major criteria including inner canthus ectopia and heterochromic iris. Sanger sequencing identified a pathogenic heterozygous c.143G>T mutation in the PAX3 gene, which involved an amino aide substitution G48V in the PAX3 protein. Six additional family members carry the same mutation. Prenatal testing showed the fetus did not carry this mutation and had a normal phenotype.

CONCLUSION: The heterozygous c.143G>T mutation in the PAX3 gene is the molecular pathological cause for WS1 in this family. Our data help expand the genotypic and phenotypic spectrum of WS1 and demonstrate that a combination of prenatal ultrasound, conventional karyotyping, and aCGH will lead to a more accurate and precise risk assessment for this disorder.
Keywords:  array comparative genomic hybridization (aCGH), gene mutation, mutation/genetics, paired box 3, prenatal diagnosis, transcription factors/genetics, Waardenburg syndrome, Waardenburg syndrome type I
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