A novel mutation in the PAX3 gene causes Waardenburg syndrome type I in an Iranian family. Issue 10 (October 2015)

• Record Type: Journal Article
• Authors: Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Farhadi, Mohammad; Bahrami, Tayyeb; Noori-Daloii, Mohammad Reza
• Is Part Of: International journal of pediatric otorhinolaryngology. Volume 79:Issue 10(2015:Oct.)
• Page Start: 1736
• Page End: 1740
• Publication Date: 2015-10
• Subjects: Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Oto-rhino-laryngologie -- Périodiques; Pédiatrie -- Périodiques; 618.9209751
• DOI: 10.1016/j.ijporl.2015.07.039
• Languages: English
• ISSNs: 0165-5876

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Objectives</title> <p id="spar0005">Sensorineural hearing impairment (HI) is one of the most frequent congenital defects, with a prevalence of 1 in 500 among neonates. Although there are over 400 syndromes involving HI, most cases of HI are nonsyndromic (70%), 20% of which follow autosomal dominant mode of inheritance. Waardenburg syndrome (WS) ranks first among autosomal dominant syndromic forms of HI. WS is characterized by sensorineural hearing impairment, pigmentation abnormalities of hair and skin and hypoplastic blue eyes or heterochromia iridis. WS is subdivided into four major types, WS1–WS4. WS1 is diagnosed by the presence of dystopia canthorum and <italic>PAX3</italic> is the only gene involved. This study aims to determine the pathogenic mutation in a large Iranian pedigree affected with WS1 in order to further confirm the clinical diagnosis.</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">In the present study, a family segregating HI was ascertained in a genetic counseling center. Upon clinical inspection, white forelock, dystopia canthorum, broad high nasal root and synophrys, characteristic of WS1 were evident. In order to clarify the genetic etiology and confirm the clinical data, primers were designed to amplify exons and exon–intron boundaries of the responsible gene, <italic>PAX3</italic> with 10 exons, followed by the Sanger DNA sequencing method.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">Genetic analysis of <italic>PAX3</italic> revealed a novel mutation in <italic>PAX3</italic> (c.1024_1040 del AGCACGATTCCTTCCAA). Our data provide genotype–phenotype correlation for the mutation in <italic>PAX3</italic> and WS1 in the studied family, with implications for genetic counseling, which necessitates detailed clinical inspection of HI patients to distinguish syndromic HI from the more common non-syndromic cases.</p> </sec> <sec> <title id="sect0025">Conclusion</title> <p id="spar0020">Our results reveal the value of phenotype-directed genetic analysis and could further expand the spectrum of <italic>PAX3</italic> mutations.</p> </sec> </abstract>