Original articleGenetic Etiology and Clinical Consequences of Complete and Incomplete Achromatopsia
Section snippets
Study Population
Patients (n = 63 probands; 36 male; mean age, 40 years) and affected family relatives (n = 18) who had been diagnosed with complete or incomplete ACHM were ascertained from various university hospitals, low vision institutes, and from the Rotterdam Eye Hospital in The Netherlands. We defined complete ACHM as the presence of poor visual acuity, congenital nystagmus, photophobia, color vision disturbances, and absent cone responses with normal rod responses on a full-field ERG. Experienced
Mutation Analysis
The frequency and relative contributions of all mutations that were detected in our study group are provided in Table 2. CNGB3 mutations were identified in 55/63 (87%) probands with ACHM (Fig 1). The most common mutation was p.T383IfsX13, a null mutation in exon 10. Probands homozygous for this mutation originated from different areas in The Netherlands and were not known to have parental consanguinity. Four probands carried other mutations in the CNGB3 gene. One of these probands carried the
Discussion
In this Dutch cohort study, we found that mutations in the CNGB3 gene are the most important causes of incomplete and complete ACHM. In the majority of the probands (55/63; 87%), we identified 2 affected alleles in this gene. No probands with 1 affected allele were detected. We found 5 different mutations, including the common p.T383IfsX13 and a novel mutation p.G348VfsX35; all mutations caused premature truncation of the protein. In only 3 probands did we detect mutations in the CNGA3 gene
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Manuscript no. 2008-1176.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Supported by the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Dr. F.P. Fischer Stichting, Gelderse Blinden Stichting, Landelijke Stichting voor Blinden en Slechtzienden (LSBS), Macula Degeneratie Fonds (MD fonds), Prof. Dr. Henkes Stichting, Research Fonds Oogheelkunde Nijmegen, Stichting Blindenhulp, Stichting Blinden-penning, Stichting Nederlands Oogheelkundig Onderzoek (SNOO), Stichting Ondersteuning Oogheelkunde's-Gravenhage (OOG), Stichting ter Verbetering van het Lot der Blinden Nederland, Stichting Wetenschappelijk Onderzoek Oogziekenhuis (SWOO).