Human Genetics

, Volume 121, Issue 3, pp 433–439

Achromatopsia: the CNGB3 p.T383fsX mutation results from a founder effect and is responsible for the visual phenotype in the original report of uniparental disomy 14

Authors

  • Wojciech Wiszniewski
    • Department of Molecular and Human GeneticsBaylor College of Medicine
  • Richard Alan Lewis
    • Department of Molecular and Human GeneticsBaylor College of Medicine
    • Department of PediatricsBaylor College of Medicine
    • Department of MedicineBaylor College of Medicine
    • Department of OphthalmologyBaylor College of Medicine
    • Department of Molecular and Human GeneticsBaylor College of Medicine
    • Department of PediatricsBaylor College of Medicine
    • Program in Cell and Molecular BiologyBaylor College of Medicine
Original Investigation

DOI: 10.1007/s00439-006-0314-y

Cite this article as:
Wiszniewski, W., Lewis, R.A. & Lupski, J.R. Hum Genet (2007) 121: 433. doi:10.1007/s00439-006-0314-y

Abstract

Achromatopsia (ACHM) or rod monochromacy is an autosomal recessive and genetically heterogeneous retinal disorder. It is characterized by a lack of color discrimination, poor visual acuity, photodysphoria, pendular infantile nystagmus, and abnormal photopic electroretinographic (ERG) recordings with preservation of rod-mediated function. Mutations in three known genes are causative; including genes for the α and β subunits of the cyclic nucleotide-gated cation channel (CNGA3 and CNGB3, respectively) and cone photoreceptor transducin—GNAT2. We investigated the prevalence of mutations in achromatopsia-causing genes in a cohort of 16 families with both clinical and electrophysiologic evidence consistent with autosomal recessive transmission, including one subject with achromatopsia and maternal isodisomy for chromosome 14. The most frequent mutation, p.T383fsX in CNGB3, accounted for 75% (18/24) of disease-associated alleles; intragenic SNPs in unrelated patients revealed transmission of a common haplotype consistent with a founder effect. Homozygous p.T383fsX mutation in CNGB3 that maps to chromosome 8 was detected in a patient with achromatopsia and systemic features associated with uniparental disomy (UPD) of chromosome 14. Two novel variants, p.R223G and p.A621E were found in CNGA3. We conclude that CNGA3 and CNGB3 mutations are responsible for the substantial majority of achromatopsia. Furthermore, the CNGB3 mutation p.T383fsX is a predominant mutation, results from a founder effect, and is responsible for the ACHM in the original clinical report of UPD 14.

Copyright information

© Springer-Verlag 2007