The cause of half of all developmental disorders is a genetic mystery

By | November 8, 2018
Pregnant woman having sonogram

Some mysteries of development are still unsolved

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“If we have more children, will they also have the disorder?” That’s the question parents ask after discovering their child has a developmental disorder – and it looks as though providing an answer is going to be even more complex than we thought.

About 1 in 100 children are born with unexplained deformities of the body, learning or behavioural difficulties – including autism – and other health problems such as heart disorders. The causes are thought to be genetic even though neither parent is affected.

How can this be? Last year, the Deciphering Developmental Disorders project, based at the Wellcome Sanger Institute in the UK, reported that nearly half of the developmental disorders in 4000 children in Europe were due to a new mutation occurring in the sperm or eggs of one parent.

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Surprising discovery

As for the rest, the leading idea was that they were due to rare recessive mutations – mutations that only have an effect if both copies of a gene have the mutation. But in a study of 6000 children in Europe with developmental disorders, the project has now shown that only 4 per cent of developmental disorders are due to recessive mutations in the protein-coding parts of genes.

In other words, around half the cases remain unexplained. “That was a surprise,” says team member Hilary Martin.

The most likely explanation, she thinks, is that the effect of many rare genetic variants depends on what other variants an individual inherits. A parent might carry a mutation without any ill-effects, but when combined with gene variants from the other parent the same mutation could have very serious effects.

The team also looked at the genes of 300 children with Pakistani ancestry who have developmental disorders. In Pakistan, it is common for people to marry cousins, which increases the chances of people inheriting two copies of a mutation and thus of developing a recessive disorder. In this group, a third of developmental disorders were due to recessive genes and a third to new mutations, but a third are still unexplained.

Journal reference: Science, DOI: 10.1126/science.aar6731

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