1Department of Ophthalmology, Rigshospitalet, Kennedy Center, Copenhagen, Denmark
2Private Genealogical Practice, Roskilde, Denmark
3Molecular Genetics Laboratory | Institute for Ophthalmic Research | Centre for Ophthalmology | University Clinics Tübingen, Germany
*Corresponding author: Thomas Rosenberg, Department of Ophthalmology, Rigshospitalet, Kennedy Center, Copenhagen, Denmark
Received Date: 10 January, 2021; Accepted Date: 10 February, 2021; Published Date: 15 February, 2021
In 1940 two Danish ophthalmologists published the largest known family with congenital total achromatopsia. The family inhabited a small island Fuur situated in a Danish fiord. In connection with the first International Congress of Human Genetics in 1956 an excursion was arranged to the island by Albert Franceschetti, for a closer characterization of the intrafamilial phenotypic variation. They also examined two brothers from an unrelated family with discordant phenotypes, complete and incomplete achromatopsia, respectively. The finding contrasted the prevailing “one gene-one disease” concept. Genealogical evidence indicates that the mutation was brought to the island by a male born about 1620. A molecular analysis of the large family revealed the most common CNGB3 mutation in Europe (biallelic c.1148delC) to be causative. In the small mainland family a different homozygous CNGB3 mutation was ascertained. A re-examination 25 years after the Fuur expedition showed unchanged phenotypes. This example illustrates problems arising due to our historically defined diagnostic taxonomy to characterize phenotypes. On the other hand, genetic classifications alone are also insufficient to meet the rising demands for genetic counseling and therapeutic inventions. A close integration of clinical and molecular genetic data has become mandatory in both research and daily practice.