Article

Nonsense mutations in the PAX3 gene cause Waardenburg syndrome type I in two Chinese patients.

Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital to Chinese General Hospital of PLA, Beijing 100037, China.
Chinese medical journal (Impact Factor: 1.02). 02/2007; 120(1):46-9.
Source: PubMed

ABSTRACT Waardenburg syndrome type I (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees.
A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an ABI_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program.
Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein.
This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations.

1 Bookmark
 · 
339 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1). WS1 was diagnosed in a 13-month-old girl according to the WS Consortium criteria. Detailed family history of the proband revealed eight affected members in three generations. Routine clinical and audiological examination and ophthalmologic evaluation were performed on eight affected and five healthy members of the study family. Dystopia canthorum was detected in all affected patients; however, a brilliant blue iris was present in five patients who also had mild retinal hypopigmentation. Genomic DNA was extracted from the peripheral blood of affected and unaffected individuals in the family as well as 50 unrelated healthy volunteers. All coding exons and adjacent intronic regions of PAX3 were sequenced directly. A novel missense heterozygous c.788T>G mutation was identified in eight patients. This nucleotide alteration was not found in unaffected members of the study family or in the 50 unrelated control subjects. The mutation causes V263G amino-acid substitution in the homeodomain of the PAX3 protein, which represents the 45(th) residue of helix 3. We identified a novel missense c.788T>G mutation in PAX3 in a family with Waardenburg syndrome with intrafamilial phenotypic heterogeneity.
    Molecular vision 01/2013; 19:196-202. · 2.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Waardenburg syndrome is a rare autosomally-inherited developmental disorder characterized by sensorineural deafness in association with pigmentary anomalies comprising various ocular features including dystopia canthorum, iris heterochromia, eyebrow flare, and fundus alterations. It is a congenital non-progressive genetic disorder that has been found to result in hearing loss, reduced vision, reduced self esteem, problems related to appearance, and decreased intellectual functioning. Case Reports: We report two familial case series that presented with the characteristic ocular findings and the systemic features of Waardenburg syndrome. The first series comprised a 32-year-old father with his two sons aged nine and six years. Two female siblings, aged 10 and eight years, both with cochlear implants, were included in the second series. Conclusion: Waardenburg syndrome manifests differently with dissimilar genetic penetration even within the same family. Some individuals will require no treatment, while others may need treatment or surgery for other abnormalities. Appropriate measures can be undertaken to negotiate the disabilities resulting from the ocular conditions associated with this syndrome. Keywords: albinotic fundus, dystopia canthorum, heterochromia iridis, sensorineural deafness, Waardenburg syndrome
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Waardenburg syndrome (WS) is characterized by the association of pigmentation abnormalities, including depigmented patches of the skin and hair, vivid blue eyes or heterochromia irides, and sensorineural hearing loss. However, other features such as dystopia canthorum, musculoskeletal abnormalities of the limbs, Hirschsprung disease, or neurological defects are found in subsets of patients and used for the clinical classification of WS. Six genes are involved in this syndrome: PAX3 (encoding the paired box 3 transcription factor), MITF (microphthalmia-associated transcription factor), EDN3 (endothelin 3), EDNRB (endothelin receptor type B), SOX10 (encoding the Sry bOX10 transcription factor), and SNAI2 (snail homolog 2), with different frequencies. In this review we provide an update on all WS genes and set up mutation databases, summarize molecular and functional data available for each of them, and discuss the applications in diagnostics and genetic counseling. Hum Mutat 31, 1–16, 2010. © 2010 Wiley-Liss, Inc.
    Human Mutation 02/2010; 31(4):391 - 406. DOI:10.1002/humu.21211 · 5.05 Impact Factor

Full-text (2 Sources)

Download
72 Downloads
Available from
May 27, 2014