Clench your left hand into a fist. What happened to your right hand when you did it?

If you’re like most people, the answer is nothing. But, surprisingly, not everyone can do this. Some people make “mirror movements”, where moving one side of the body, particularly the hands, causes the other to move unintentionally. Clench the left fist, and the right one closes too. Doing things like playing the piano or typing are very difficult. In 2002, a Chinese man with the disorder failed to get into the military because he couldn’t use the monkey bars.

Young children sometimes make mirror movements but they almost always grow out of it by the age of 10. The only exceptions tend to be people with rare genetic disorders of the nervous system, like Klippel-Feil and Kallmann syndromes. Now, Myriam Srour from the University of Montreal has found that a single faulty gene can cause the condition.

She studied a large French Canadian family with four generations of members who had been making mirror movements from birth. Not everyone was affected, and the pattern of the disorder strongly suggested that a single dominant genetic fault was responsible. Srour tracked it down by comparing the genomes of affected and normal family members, and her search led her to a short area on the 18th chromosome, which contained three genes.

One of these genes is called DCC and it turned out to be the true culprit behind the disorder. In the Canadia family, those who make mirror movements have a version of DCC with a single altered DNA ‘letter’. This tiny fault means that the protein encoded by DCC is manufactured with a missing chunk. That chunk happens to include many of the most important segments of the DCC protein, which, in its abridged form, is completely useless.

Srour found this mutation in every case of mirror movements, and never in 760 unrelated people whose left and right sides are typically independent. To confirm DCC’s role, she turned to an Iranian family, many of who also demonstrated the quirk from birth. She sequenced their DCC genes and again, she found that those who make mirror movements had broken copies. In this case, the mutation was different but the result was the same – a shortened and ineffectual protein.

It’s not just humans who are affected in this way. If mice have mutated and shortened copies of DCC, they too show mirror movements and they move with a distinctive hopping gait. These strains are affectionately known as Kanga mice. If they lack any copies of the gene entirely, their problems are more severe. The gap between the brain’s hemispheres doesn’t develop properly and the fibres that connect the two halves– the corpus callosum – are fewer in number and misrouted.

These mutant mice hint at DCC’s role. The DCC protein is a docking bay (a receptor) for another protein called netrin-1, whose role is to guide the neurons of the developing nervous system across the midline of the body. Its name even comes from the Sanskrit word “netr”, meaning “one who guides”. But this neural shepherd can’t stick to broken DCC proteins and without its good work, the neuronal connections between the body’s two halves don’t form properly.

Reference: Science http://dx.doi.org/10.1126/science.1186463