title: Genetic analysis of an Indian family with members affected with Waardenburg syndrome and Duchenne muscular dystrophy.
abstract: OBJECTIVE
  Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentation defects of the eye, skin, and hair. It is caused by mutations in one of the following genes: PAX3 (paired box 3), MITF (microphthalmia-associated transcription factor), EDNRB (endothelin receptor type B), EDN3 (endothelin 3), SNAI2 (snail homolog 2, Drosophila) and SOX10 (SRY-box containing gene 10). Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the DMD gene. The purpose of this study was to identify the genetic causes of WS and DMD in an Indian family with two patients: one affected with WS and DMD, and another one affected with only WS.
  
  
  METHODS
  Blood samples were collected from individuals for genomic DNA isolation. To determine the linkage of this family to the eight known WS loci, microsatellite markers were selected from the candidate regions and used to genotype the family. Exon-specific intronic primers for EDN3 were used to amplify and sequence DNA samples from affected individuals to detect mutations. A mutation in DMD was identified by multiplex PCR and multiplex ligation-dependent probe amplification method using exon-specific probes.
  
  
  RESULTS
  Pedigree analysis suggested segregation of WS as an autosomal recessive trait in the family. Haplotype analysis suggested linkage of the family to the WS4B (EDN3) locus. DNA sequencing identified a novel missense mutation p.T98M in EDN3. A deletion mutation was identified in DMD.
  
  
  CONCLUSIONS
  This study reports a novel missense mutation in EDN3 and a deletion mutation in DMD in the same Indian family. The present study will be helpful in genetic diagnosis of this family and increases the mutation spectrum of EDN3.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
authors.forename: Saketh
authors.initials: S
authors.lastname: Kapoor
authors.forename: Parayil Sankaran
authors.initials: PS
authors.lastname: Bindu
authors.forename: Arun B
authors.initials: AB
authors.lastname: Taly
authors.forename: Sanjib
authors.initials: S
authors.lastname: Sinha
authors.forename: Narayanappa
authors.initials: N
authors.lastname: Gayathri
authors.forename: S Vasantha
authors.initials: SV
authors.lastname: Rani
authors.forename: Giriraj Ratan
authors.initials: GR
authors.lastname: Chandak
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D003241:Consanguinity; D016189:Dystrophin / Q000235:genetics*; D019334:Endothelin-3 / Q000235:genetics*; D005091:Exons; D005808:Genes, Recessive; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D007194:India; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D060885:Multiplex Polymerase Chain Reaction; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D035781:Siblings; D014849:Waardenburg Syndrome / Q000150:complications / Q000235:genetics*
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D019334:Endothelin-3