Monogenic defects responsible for intellectual disability and related disorders

For over 15 years, genome research has focussed – largely unsuccessfully – on the quest for common genetic risk factors for widespread diseases and conditions, such as diabetes, high blood pressure, schizophrenia and cancer. One of the reasons for this is that many different genetic disorders can be hidden behind these diseases, and not uncommonly defects in individual genes are involved.

However, most of these genetic defects are still unexplained. Researchers at the Max Planck Institute for Molecular Genetics in Berlin and their colleagues in Iran have now succeeded in identifying 50 hitherto unknown genetic causes of intellectual disability. Moreover, there is good reason to believe that several of these new genetic defects are also responsible for related disorders, such as autism, schizophrenia and epilepsy.

To date, almost 7,000 'monogenic' diseases are known, and the corresponding genetic defect identified for around half of them. Around 17 percent of children who are admitted to hospital suffer from these diseases, and the percentage of total healthcare costs generated by their treatment is considerably higher. Nonetheless, many monogenic diseases are still unknown. They often remain undiagnosed as they involve cases that are not associated with an identifiable family history or patients with supposedly complex common diseases and conditions.

An international consortium, of which the Max Planck Institute for Molecular Genetics is a prominent member, has now discovered 50 hitherto unknown genetic causes of intellectual disability in children. This disorder only arises if the – usually healthy – parents have a predisposition for a certain genetic defect and both pass on a mutated copy of the same gene to their children. Very little has been known about such 'recessive' genetic defects up to now, as the scientists need families with several affected members, in other words very large families, to explain them.

Such families are rare in Germany and other Western countries; however, this is not the case among the populations of the Near and Middle East. Moreover, many parents in these countries are related and this could explain why intellectual disability is around three times more common there than in Germany. Therefore, the Max Planck researchers are collaborating closely with a research centre in Iran.

''We all carry genetic defects in us. However, there is a much higher risk that the same genetic defect is involved in diseases suffered by blood relatives,'' says Hilger Ropers. The sick children of blood-related parents have two identical copies of the responsible genetic defect and the surrounding chromosome sections are also completely identical. This makes it easier for the researchers to find the defective gene.