title: Intrafamilial variability in syndromic microphthalmia type 5 caused by a novel variation in OTX2.
abstract: Anophthalmia/microphthalmia/coloboma (MAC) spectrum encompasses the most severe malformations of the eye. Together, they have an incidence of 2 in 10,000 births and can be unilateral or bilateral. These disorders are genetically heterogeneous.
  
  
  
  We ascertained a large three-generation family with multiple members showing variable phenotypes of syndromic microphthalmia. Exome sequencing was performed for the proband and his affected maternal aunt. Targeted sequencing of OTX2 gene was performed for other family members.
  
  
  
  Variable clinical presentation in the form of unilateral microphthalmia and bilateral microphthalmia as well as nonpenetrance were noted. Exome sequencing revealed a novel heterozygous variant c.278G>T (p.W93L) in OTX2 in the proband. All affected members as well as the unaffected mother of the proband carried the same variant.
  
  
  
  Syndromic microphthalmia due to mutations in OTX2 can present with significant intrafamilial phenotypic variability.
authors.affiliation: a Department of Medical Genetics , Kasturba Medical College, Manipal University , Manipal , India.
authors.forename: Puneeth H
authors.initials: PH
authors.lastname: Somashekar
authors.affiliation: a Department of Medical Genetics , Kasturba Medical College, Manipal University , Manipal , India.
authors.forename: Anju
authors.initials: A
authors.lastname: Shukla
authors.affiliation: a Department of Medical Genetics , Kasturba Medical College, Manipal University , Manipal , India.
authors.forename: Katta M
authors.initials: KM
authors.lastname: Girisha
mesh_terms: D000328:Adult; D002648:Child; D059472:Exome / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008850:Microphthalmos / Q000235:genetics*; D009154:Mutation; D051857:Otx Transcription Factors / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: C497659:OTX2 protein, human; D051857:Otx Transcription Factors
keywords: Anophthalmia; OTX2 gene; bilateral clinodactyly; microphthalmia; optic nerve hypoplasia