title: A novel homozygous variant in the SMOC1 gene underlying Waardenburg anophthalmia syndrome.
abstract: Waardenburg anophthalmia syndrome (WAS), also known as ophthalmo-acromelic syndrome or anophthalmia-syndactyly, is a rare congenital disorder that segregates in an autosomal recessive pattern. Clinical features of the syndrome include malformation of the eyes and the skeleton. Mostly, WAS is caused by mutations in the SMOC-1 gene.
  
  
  
  The present report describes a large consanguineous family of Pakistani origin segregating Waardenburg anophthalmia syndrome in an autosomal recessive pattern. Genotyping followed by Sanger sequencing was performed to search for a candidate gene.
  
  
  
  SNP genotyping using AffymetrixGeneChip Human Mapping 250K Nsp array established a single homozygous region among affected members on chromosome 14q23.1-q24.3 harboring the SMOC1 gene. Sequencing of the gene revealed a novel homozygous missense mutation (c.812G>A; p.Cys271Tyr) in the family.
  
  
  
  This is the first report of Waardenburg anophthalmia syndrome caused by a SMOC1 variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SMOC-1 in causing WAS.
authors.affiliation: a Department of Biochemistry, Faculty of Biological Sciences , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Asmat
authors.initials: A
authors.lastname: Ullah
authors.affiliation: a Department of Biochemistry, Faculty of Biological Sciences , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Umair
authors.affiliation: a Department of Biochemistry, Faculty of Biological Sciences , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Farooq
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: b Chandka Medical College, Shaheed Mohtarma Benazir Bhutto Medical University , Larkana , Pakistan.
authors.forename: Dost
authors.initials: D
authors.lastname: Muhammad
authors.affiliation: c Center for Genetics and Inherited Diseases, Taibah University , Medina , Saudi Arabia.
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.affiliation: a Department of Biochemistry, Faculty of Biological Sciences , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003241:Consanguinity; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D060005:Genotyping Techniques; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D015676:Osteonectin / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: D015676:Osteonectin; C468135:SMOC1 protein, human
keywords: Missense mutation; SMOC1 gene; SNP genotyping, Waardenburg anophthalmia syndrome