Mutations behind lethal congenital disease common in Arabs revealed

Meckel–Gruber Syndrome (MKS) is a complex congenital disease, caused by defective cilia and involving multiple malformations of the brain, kidneys and liver; it is lethal in all cases. In most populations it is rare, with a prevalence of less than 1:20,000.

In Finland, however, it has an estimated prevalence of 1:9,000 births, and in Arab populations in which there are high rates of consanguineous families it is even more common. Despite this, there has been little research on the disease in this particular ethnic group.

Researchers have previously identified 10 genes that are mutated in MKS. All of them encode components of cilia, which are slender, hair-like structures that project from the surface of nearly all mammalian cells and have vital roles in many cellular functions.

A team led by Fowzan Alkuraya of the King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, has performed the largest and most comprehensive genetic study of MKS in Arabs yet. By analysing the genomes of individuals from 18 consanguineous Arab families with MKS, they identified three candidate genes, each of which may cause MKS when mutated¹.

All three of the newly identified genes encode proteins that are involved in the development or function of cellular cilia. The findings thus expand the number of ciliary genes that are thought to cause MKS when mutated. They also reveal that MKS has multiple genetic causes, and suggest that the 10 previously reported genes, together with the three identified in the study, account for the overwhelming majority of cases of the condition.

Alkuraya explains that screening for these genes can help parents avoid having more affected children. "There are MKS families who are now undergoing early prenatal diagnosis to see if their current pregnancy is affected to make informed reproductive choices. Some [who are having IVF] are opting for pre-implantation genetic diagnosis instead."

Alkuraya hopes to eventually characterize the role of the genes identified in the study further, as well as identify any other genes involved in MKS, to give a full picture of the disease.

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