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Markus N Preising, Anna-Maria Zuliani, Birgit Lorenz; A Novel Candidate Gene for Complete Achromatopsia. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2781.
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© ARVO (1962-2015); The Authors (2016-present)
In an eight generation German family with two branches and three patients (mother, son, cousin) affected with ACHM CNGB3 was identified as the underlying gene in the son and his distant cousin. In the mother CNGB3 was excluded. Here were present our results on identification of a novel gene underlying achromatopsia (ACHM).
The patients were examined by best corrected visual acuity (BCVA), Ganzfeld ERG (ffERG), Goldmann visual field (GVF), Lanthony panel D15 color test, and fundus photography.Whole exome (WES) next-generation sequencing was done in the son and the mother.Sequence changes in candidate genes were directly sequenced for segregation analysis in the family. Six further patients were sequenced for mutations in the most probable candidate gene.
The clinical data of the three patients indicated complete ACHM as to BCVA: 0,1 - 0,2, cone responses in ffERG below threshold and unremarkable fundus appearance even up to the age of 37 y. Rod responses in ffERG were unremarkable in the son and cousin while rod function was reduced unilateral in the mother at age 37 y.After identification of a homozygous common c.1148delC mutation in CNGB3 in the affected cousin (the latest descendant of branch 1, suspected consanguinity of the parents) and the son (affected descendant of consanguineous parents in branch 2). CNGB3 c.1148del was heterozygous in the mother and no other CNGB3 mutation was identifed.By WES of the maternal DNA possible disease causing sequence variations in the mother at a population frequency below 0.1 were identified in 205 genes. One hundred ninety eight genes were ruled out by segregation analysis or by carrying frequent sequence variations. From the remaining 7 genes expression in the retina has been reported for two genes. Finally, we identified a compound heterozygous pair of deleterious mutations in the mother in a gene for a photoreceptor synapse protein. The son was heterozygous for one of the mutations and the cousin was excluded in this gene like six further patients with ACHM who were previously excluded for the most common achromatopsia genes.
We identified compound heterozygous deleterious mutations in a photoreceptor synapse component in a patient presenting with ACHM up to her mid-thirties and additional rod involvement thereafter. Exclusion in a limited set of ACHM patients suggests either rare involvement of this gene in ACHM or an involvement in a different cone-rod degeneration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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