Molecular genetic cause of achromatopsia in two patients of Czech origin.

Abstract

INTRODUCTION:

Achromatopsia is an autosomal recessive retinal disorder with an estimated prevalence ranging from 1 in 30.000 to 50.000. The disease is caused by mutations in six different genes. The aim of the study was to perform molecular genetic analysis in 11 unrelated probands with a clinical diagnosis of achromatopsia and to describe clinical findings in those that were found to carry biallelic pathogenic mutations.

METHODS:

All probands and their parents underwent ophthalmic examination. Mutation detection was performed using Sanger sequencing of CNGB3 exons 6, 7, 9-13, which have been found to harbour most disease-causing mutations in patients with achromatopsia of European origin.

RESULTS:

Three known pathogenic variants in CNGB3 were identified in 2 probands. Proband 1 was a compound heterozygote for the c.819_826del; p.(Arg274Valfs*13) and c.1006G>T; p.(Glu336*). Proband 2 carried the c.1148del; p.(Thr383Ilefs*13) in a homozygous state. The best corrected visual acuity in proband 1 (aged 19 years) was 0.1 in both eyes, in proband 2 (aged 8 years) 0.05 in the right eye and 0.1 in the left eye. Both individuals had nystagmus, photophobia, and absence of colour discrimination. Fundus examination appeared normal however spectral-domain optical coherence tomography revealed subtle bilaterally symmetrical structural changes in the fovea.

CONCLUSION:

Molecular genetic analysis of Czech patients with achromatopsia was performed for the first time. Identification of disease-causing mutations in achromatopsia is important for establishing an early diagnosis, participation in clinical trials assessing gene therapies and may be also used for preimplantation genetic diagnosis.

• Authors: L Hlavatá, Ľ Ďuďáková, J Moravíková, A Zobanová, B Kousal, P Lišková
• Journal: Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti (Cesk Slov Oftalmol) Vol. 75 Issue 5 Pg. 272-276 ( 2019) ISSN: 1211-9059 [Print] Czech Republic
• Vernacular Title: Molekulárně genetická příčina achromatopsie u dvou pacientů českého původu.
• PMID: 32397729 (Publication Type: Journal Article)

Chemical References

• CNGB3 protein, human
• Cyclic Nucleotide-Gated Cation Channels

Topics

• Child
• Color Vision Defects (genetics)
• Cyclic Nucleotide-Gated Cation Channels (genetics)
• Czech Republic
• DNA Mutational Analysis
• Humans
• Mutation
• Pedigree
• Tomography, Optical Coherence
• Young Adult