Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations

Genet Med. 2011 Nov;13(11):978-81. doi: 10.1097/GIM.0b013e31822623d5.


Purpose: Designating mutations as recessive or dominant is a function of the effect of the mutant allele on the phenotype. Genes in which both classes of mutations are known to exist are particularly interesting to study because these mutations typically define distinct pathogenic mechanisms at the molecular level.

Methods: We studied two consanguineous families with different eye phenotypes and used a combination of candidate gene analysis and homozygosity mapping to identify the underlying genetic defects.

Results: In one family, a novel BFSP2 mutation causes autosomal recessive diffuse cortical cataract with scattered lens opacities, and in another, a novel PITX3 mutation causes an autosomal recessive severe form of anterior segment dysgenesis and microphthalmia.

Conclusion: We show that BFSP2 and PITX3, hitherto known to cause eye defects only in a dominant fashion, can also present recessively. The likely null nature of both mutations and lack of manifestation in heterozygotes strongly argues for a mechanism other than loss of function in the previously reported dominant mutations in these two genes. Thus, study of consanguineous populations has the additional advantage of not only identifying novel recessive genes but also defining the mutational mechanism of dominant disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cataract / genetics
  • Consanguinity
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Family Health
  • Female
  • Genes, Recessive
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Male
  • Microphthalmos / genetics
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Transcription Factors / genetics*


  • Eye Proteins
  • Homeodomain Proteins
  • Intermediate Filament Proteins
  • Transcription Factors
  • homeobox protein PITX3
  • phakinin