Study Discovers Gene Mutation That Makes Familiar Faces Unrecognizable

One of life’s simple pleasures is unexpectedly bumping into a friend or family member in a busy place like a train station or market. Recognizing a familiar face in an unexpected setting brings joy to most of us.

We owe this ability to our MCTP2 gene. According to research published in the journal Genetics by a team led by Ye Rao from Capital Medical University in Beijing, a mutation in this gene can severely impair our ability to recognize faces.

People with this mutated gene take much longer to recognize those they should know well, such as spouses, siblings, and children. They also often mistake strangers for familiar people.

This condition is known as prosopagnosia, or face blindness, and affects about 1.8-2.9% of the global population. Prosopagnosia is a type of visual agnosia, which is the inability to identify everyday objects just by looking at them.

The MCTP2 gene is the first gene found to be necessary for this higher form of visual social cognition in humans.

Face Recognition and the MCTP2 Gene

The researchers studied a family of 35 people across three generations. The oldest members were all over 60 years old. Nine family members had daily problems recognizing faces and performed poorly on a standardized face recognition test. Another nine did well on the tests but still had trouble recognizing faces.

The remaining 17 family members, including nine who married into the family, had no issues recognizing faces and performed normally on the tests.

By mapping the family tree, the researchers inferred that a great-grandparent of the eldest generation carried the mutation. This mutation was then passed down to their children and grandchildren.

When examining the genomes of the affected family members, the researchers found that they all had the same segment of chromosome 15 altered. We inherit two copies of each chromosome, one from each parent, making up 23 pairs of chromosomes in total.

By sequencing the genomic DNA, the researchers discovered that the MCTP2 gene in this segment had a mutation. This mutation caused one amino acid in the protein encoded by the MCTP2 gene to be replaced by another. This specific mutation was not found in any of the hundreds of thousands of human genome sequences stored in various databases, making it unique to this family.

Validation from Population Studies

To confirm that face blindness was caused by this specific mutation, the researchers conducted a population study. They recruited 2,904 individuals (743 males and 2,161 females, all around 19 years old) to complete an online questionnaire that included elements of the face recognition test. Seventy-eight individuals scored very poorly, deviating by two standard deviations or more from the average score.

The researchers sequenced the genomes of 75 of these poor scorers and found that seven of them had one of five other sequence alterations in the MCTP2 gene. This showed that unrelated individuals who performed poorly on face recognition tests were more likely to have independent mutations in the MCTP2 gene compared to the general population.

Additionally, the team found that the first-degree relatives (parents, children, or siblings) of these individuals, who shared their mutation, also had face recognition impairments.

These findings implicated the MCTP2 gene in face recognition.

For the 68 others who did poorly on the test but had non-mutated MCTP2 genes, some might have had mutations in other genes related to face recognition. Others might have had face recognition problems due to infection or injury, and some might have been false positives.

A questionnaire-based screen is unlikely to be 100% accurate in identifying individuals with face recognition deficits; even ’normal’ face recognizers might perform poorly on a questionnaire for various reasons.

In the brain, the right middle fusiform gyrus, also known as the fusiform face area (rFFA), is activated during facial recognition. When the researchers used functional magnetic resonance imaging to study individuals with different MCTP2 mutations, they found abnormal responses in the rFFA.

When a Glove Becomes a Puzzle

It’s hard for most of us to imagine living with visual agnosia. In his 1985 book ‘The Man Who Mistook His Wife for a Hat,’ neurologist and writer Oliver Sacks recounted case histories of some of his patients. One patient, Dr. P., was a distinguished musician and teacher with visual agnosia caused by a brain tumor.

When Dr. P. was given a glove and asked what it was, he described it as “a continuous surface infolded on itself, with five outpouchings…” He thought it was a change purse for coins. He couldn’t tell his foot from his shoe and mistook water hydrants and parking meters for children, patting them on the head. He even mistook his wife for a hat.

Despite his condition, Dr. P. continued to teach music until the end of his life.

With the discovery of the MCTP2 gene’s role, our confusion about visual agnosia can start to clear up. Both Dr. Sacks and Dr. P. would have been pleased with this progress.

D.P. Kasbekar is a retired scientist.