Recessive disorder impairing eyesight has been discovered

A new gene, MARK3, has been identified as being responsible for a genetic disorder.

Researchers form the University of Geneva (UNIGE) Switzerland, worked in collaboration with scientists from Liaquat University, Pakistan and the USA to investigate the abnormality which prevents the eyes in children from developing properly.

Each member of 200 consanguineous affected families in Pakistan, had their genomes analysed. Each family had 2 healthy children and 3 with the genetic abnormality.  

“The aim was to see which gene had mutations on two copies in the affected children, on one copy in the parents and 1 or zero copies in the healthy children,” said Muhammad Ansar, a researcher in the department of Genetic Medicine and Development at UNIGE.  

After the genome analysis, scientists confirmed the findings by modifying the homologous gene in drosophila flies. This resulted in abnormal eye development in the flies.

Researchers carried out bioinformatic analyses along with genetic segregation to identify the mutations of each gene in the healthy and affected children and their parents, isolating the pathogenic mutations in the MARK3 gene as being responsible for this recessive disorder.

The identification of this gene will enable the scientists to understand the mechanism of the disease, providing diagnostic services and pushing efforts for personalised treatments.

With 20,000 genes in the genome, only 4,141 genes have been identified as causing genetic abnormalities. In reality, any gene can contribute to abnormalities, which leaves around 16,000 genes potentially causing disorders.

Monogenic genetic disorders can be dominant or recessive, with dominant only needing one version of the allele to cause the disease, such as Huntington’s disease. Recessive disorders need both alleles (one from the mother and one from the father) in order for the disease to be presented. Offspring with only one allele are carriers and can pass on the disease to their children.

This discovery means that a new recessive genetic disease can be accurately diagnosed.

“We can now concentrate on studying the mechanisms behind the disorder with the aim of finding a treatment,” said Professor Stylianos Antonarakis, a professor Emeritus in UNIGE’s Faculty of Medicine.

“Our collaboration with Pakistan helped us identify about an additional 30 genes that are potentially responsible for recessive genetic disorders. We are currently refining the analyses so that, little by little, we can reduce the total number of 16,000 genes whose mutations and disorders are yet to be discovered,” conclude the researchers at Geneva.

The findings were published in Human Molecular Genetics.