Gene mutation turns familiar faces into strangers, study finds

Gene mutation turns familiar faces into strangers, study finds

The global prevalence of prosopagnosia, or face blindness, is estimated to be 1.8-2.9% in the general population. It is a form of visual agnosia, or the inability to recognize everyday objects by mere sight. Representative photo.

The global prevalence of prosopagnosia, or face blindness, is estimated to be 1.8-2.9% in the general population. It is a form of visual agnosia, or the inability to recognize everyday objects by simply looking at them. Representative photo. | Photo credit: Stewart McLean/Unsplash

A simple pleasure, often taken for granted, is bumping into a friend or relative at a railway station or a market. Recognising a familiar face in an unfamiliar context or a crowded place brings immense joy to most of us.

We should thank our MCTP2 gene for this ability. Research published in this month's issue of the magazine GeneticsWhen this gene is mutated, the ability to recognise faces is severely impaired, according to the study by researchers led by Ye Rao of Capital Medical University in Beijing.

Individuals with the misfortune of carrying the mutant gene took far longer than the socially acceptable time to recognise people they were familiar with – such as spouses, siblings and children – while they were confused when mistaking strangers for acquaintances.

This disorder is called prosopagnosia or face blindness. Its worldwide prevalence is estimated to be 1.8-2.9% in the general population. Prosopagnosia is a form of visual agnosia, or the inability to recognize everyday objects by simply looking at them.

The MCTP2 gene is thus the first gene found to be required for a higher form of visual social cognition in humans.

Face recognition and a gene

The researchers identified a family of 35 individuals spanning three generations. All members of the eldest generation were over 60 years old. Nine members of the family had daily problems recognizing faces. They also performed very poorly on a standardized face recognition test. The other nine performed normally on the tests, yet still had difficulty recognizing faces.

The remaining 17 – nine of whom had married within the family – performed normally on the test and had no difficulty recognising faces.

By charting a family tree, the researchers inferred that the mutation must have occurred in the great-grandparents of the eldest generation. The eldest members then passed the mutation on to their affected children and grandchildren.

Examining the genomes of the affected family members revealed that they had all inherited the same genome segment in one copy of their chromosome number 15. Recall that we inherit two copies of each chromosome, one from each parent, and so each of us has 23 pairs of chromosomes.

By sequencing genomic DNA, the researchers found that the MCTP2 gene located in this segment was altered by a mutation. As a result, one amino acid in the protein encoded by the MCTP2 gene was replaced by another. The researchers did not find this mutation in any of the hundreds of thousands of human genome sequences stored on various databases.

That is, this mutation was new and specific to this family.

Validation from population studies

But how did the researchers conclude that the facial disability was indeed caused by this mutation, and not by some other mutation in the candidate genome segment?

They arrived at their conclusions based on population investigations. The researchers recruited a group of 2,904 individuals (743 men and 2161 women, all around 19 years of age) to answer an online questionnaire. The questionnaire included elements of a face recognition test. Seventy-eight individuals scored very poorly: that is, their scores deviated from the mean score by two standard deviations or more.

The researchers sequenced the genomes of 75 people with poor scores and found that seven of them had one of five other sequence changes in the MCTP2 gene. This showed that unrelated individuals who performed very poorly in face recognition tests were more likely to have independent mutations in the MCTP2 gene than the general population.

Additionally, the team found that first-degree relatives of individuals who had the mutation, such as parents, children, or siblings, also showed facial recognition deficits.

These findings showed that the MCTP2 gene aids in facial recognition.

As for the 68 other people who did poorly on the test but had no change in their MCTP2 gene: Some of them may have had changes in other genes involved in face recognition. Others may have had trouble recognizing faces because of infection or injury. And still others may have actually had false positives.

Questionnaire-based screens are unlikely to achieve 100% specificity in identifying individuals with face recognition impairments; for external reasons, even 'normal' face recognition devices may perform poorly on questionnaires.

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

When the glove becomes a riddle

It is difficult for most of us to imagine what it is like to live with visual agnosia. In his bestselling 1985 book The Man Who Mistook His Wife for a Hat, the brilliant neurologist and author Oliver Sacks (1933-2015) recounted the case histories of some of his patients. Dr P. was a distinguished musician and teacher, and had visual agnosia caused by a brain tumor.

When Dr. P. was given the glove and asked what it was, he described it as “a continuous surface, folded in on itself, with five external pouches…” He imagined it as a purse for coins. When asked to put on a shoe, he could not separate his foot from his shoe. He mistook water hydrants and parking meters on the street for children and patted them on the head. And he mistook his wife for a hat.

Dr. Sachs was surprised how such a man could work as a teacher in a music school. Nevertheless, Dr. P. taught music until the last days of his life.

The discovery of MCTP2's role should give us the first molecular glimpse of what is really going on in the troubled brain, alleviating our helpless bewilderment about visual agnosia. Both Dr. Sachs and Dr. P. would have been delighted by this progress.

DP Kasbekar is a retired scientist.

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