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Complex genetic analysis and skin from the laboratory provide proof

Extremely dry, scaly and highly keratinized skin: these are the typical characteristics of so-called ichthyoses. This heterogeneous group of keratinization disorders is a rare hereditary disease. Causative genetic defects have already been identified for individual forms of ichthyosis. Now researchers led by Prof. Dr. Dr. Judith Fischer, Medical Director of the Institute for Human Genetics at the Medical Center - University of Freiburg, have identified a new gene whose loss causes ichthyosis. Using a three-dimensional piece of skin grown in the laboratory, the cells of which were genetically altered, they proved that the gene alteration is actually responsible for the disease. The tissue produced by cell culture showed comparable characteristics to the skin of patients with ichthyosis. The findings provide important insights into the development of healthy skin and could serve as the basis for new therapeutic approaches for ichthyosis. The study was published on June 1, 2017 in The Amerian Journal of Human Genetics.

The researchers found the gene errors with the help of a complex analysis known as 'whole exome sequencing'. This involves checking the entire protein-coding genome, the exome, for unusual abnormalities. The errors discovered in this way, also known as mutations, were located in the SULT2B1 gene, which is involved in cholesterol metabolism and is essential for the correct functioning of the skin. The gene mutation leads to a loss of function of SULT2B1.

To test whether the loss of SULT2B1 leads to the corresponding disease symptoms, the scientists cultivated a three-dimensional skin in the laboratory whose cells had no active SULT2B1. After two weeks, the researchers saw under the microscope that the skin cells proliferated too much, developed insufficiently and keratinized excessively.

Original title of the study: Mutations in SULT2B1 cause autosomal recessive congenital ichthyosis in humans

DOI: 10.1016/j.ajhg.2017.05.007http://www.cell.com/ajhg/abstract/S0002-9297(17)30194-5

Link to the study: www.cell.com/ajhg/abstract/S0002-9297(17)30194-5

Caption: Left: Skin of a healthy person; Right: Both the layer of living (blue) and dead (green) skin cells is heavily thickened in patients with ichthyosis.
Image source: AJHG/J. Fischer

Contact:
Prof. Dr. Dr. Judith Fischer
Medical Director
Institute for Human Genetics
Medical Center - University of Freiburg
Phone: 0761 270-70500
judith.fischer@uniklinik-freiburg.de