Wissinger Lab

Molecular Genetics Laboratory

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Scientific Results

  1. Based on the in-depth genetic analysis of our large collection of families with autosomal dominant optic atrophy (ADOA) we could demonstrate that large deletions or duplications at the OPA1 gene locus are present in up to 15% of the ADOA families which emphasizes the importance of copy number variation detection technologies for the genetic testing in ADOA. This study also led to the elucidation of the OPA1 gene defect in an ADOA family that has been described in the 1950s by the German ophthalmologist Wolfgang Jäger in one of the first descriptions of this disease in the medical literature.
  2. Moreover, in a close cooperation with colleague from the Dept. of Neurology in Bologna/Italy we have been able to map a new locus for a clinically complex form of ADOA on human chromosome 16, though the gene itself is currently unknown and subject of ongoing research.
  3. For autosomal recessively inherited achromatopsia (rod monochromacy), a subject of intense research for many years, we have been able to identify all disease-associated genes - CNGA3, CNGB3, GNAT2, PDE6C, PDE6H - and only recently the now sixth disease gene ATF6. This is very interesting, as all other achromatopsia genes are exclusively expressed in the cone photoreceptor and there encode for proteins of the phototransduction, while ATF6 is expressed in every cell of the body and is known for its function in ER (endoplasmatic reticulum) stress regulation. Why and how a defect in ATF6 exclusively causes a cone photoreceptor defect is to date subject of our research.
  4. In this context, we have collected - also through international collaboration - the world's largest patient and DNA collection for this rare disorder.
  5. In the same context, using recombinantly expressed PDE5/6C chimeric protein we could confirm the functional deficiency of certain PDE6C missense mutations and characterize their altered biophysical properties.
  6. In our series of investigations of mutants of the cone CNG channel we have described for the first time the functional consequences and altered biophysical properties of mutations in the pore domain of the A3 subunit of the channel.