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A Novel Mutation of PAX3 on a Large Chinese Family with
Waardenburg Syndrome
Juan Liu1, Xiangfu Meng2, Caixia Sun2, Jingmin Wen1, Yong Gao1, Jing Yu Liu1*
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life
Science and Technology, Center for Human Genome Research, Huazhong University
of Science and Technology, 430074, Wuan, Hubei, P. R. China;2 People Hospital of
Xiajin, Xiajin, Shandong, 253200, China
Objectives: Waardenburg syndrome (WS) is an autosomal dominant and genetically
heterogeneous disorder characterized by manifests with sensorineural deafness and
pigmentation defects of the hair, skin, and iris. It is classified into four types depending
on the presence or absence of additional symptoms, WS1, WS2, WS3 and WS4. WS1
and 3 are due to mutations in the PAX3 gene. WS2 are associated with mutations of
MITF, SNAI2, and SOX10, in addition, there are two loci, 1p21-p13.3 and 8p23. WS4
can result from mutations in EDNRB and EDN3.Methods: Linkage analysis was used
to identify the chromosomal location of the disease gene, direct DNA sequence analysis
was used for mutation detection and restriction fragment length polymorphism (RFLP)
analysis was checked this mutation in the family. Results: A large five-generation
Chinese family from Shandong Provience with autosomal dominant WS1 have
identified and characterized. Linkage analysis was identified with marker D2S126,
which is located near Pax3 gene. The PAX3 gene is closely linked to the disease of this
family. Mutational analysis of all exons and exon-intron boundaries of PAX3, a novel
mutation c.272A>G in the proband was found. RFLP analysis showed that the mutation
is in all patients, but not in all normal individuals and 200 normal controls. The
mutation occurs at a highly conserved residue in the paired domain (PD) of PAX3,
which is the DNA binding domain. Conclusion: These results indicate that the
c.272A>C mutation of PAX3 gene probably causes WS in the family and expand the
mutation spectrum of PAX3 gene.
Key Words: Waardenburg syndrome, PAX3, Linkage analysis, Mutation analysis
*Correspondence to: Dr. J. Y. Liu, liujy@mail.hust.edu.cn