Human Genetics of Face Recognition: Discovery of MCTP2 Mutations in Humans with Face Blindness (Congenital Prosopagnosia)

Face recognition is important for both visual and social cognition. While congenital prosopagnosia (CP) or face blindness has been known for seven decades and electrophysiological studies have characterized face specific neurons for half a century, no molecular analyses have been undertaken. Here we report results after 14 years of research combining classic genetics and modern genomics involving over 7000 subjects. From a large family with 18 CP members, we uncovered a fully co-segregating private mutation in the MCTP2 gene which encodes a calcium binding transmembrane protein expressed in the central nervous system. More rare mutations in MCTP2 were detected in CP families screened from a cohort of 2904 college students and were also associated with CPs in a second cohort of 1928. In a third cohort of 1757, face recognition was different between 14 carriers with a frameshift mutation S80fs in MCTP2 and 19 non-carrying volunteers. 6 families including one with 10 members showed the S80fs-CP correlation. Functional magnetic resonance imaging (fMRI) indicates that impaired recognition of individual faces by CPs with the MCTP2 mutations is associated with inability to recognize the same faces in the right fusiform face area (rFFA). Our results have revealed the genetic predisposition of MCTP2 mutations in CP, 74 years after the initial report of CP. This is the first time a gene required for a higher form of visual social cognition was found in humans.

Spatial Integration in Normal Face Processing and Its Breakdown in Congenital Prosopagnosia

Congenital prosopagnosia (CP), a life-long impairment in face processing that occurs in the absence of any apparent brain damage, provides a unique model in which to explore the psychological and neural bases of normal face processing. The goal of this review is to offer a theoretical and conceptual framework that may account for the underlying cognitive and neural deficits in CP. This framework may also provide a novel perspective in which to reconcile some conflicting results that permits the expansion of the research in this field in new directions. The crux of this framework lies in linking the known behavioral and neural underpinnings of face processing and their impairments in CP to a model incorporating grid cell–like activity in the entorhinal cortex. Moreover, it stresses the involvement of active, spatial scanning of the environment with eye movements and implicates their critical role in face encoding and recognition. To begin with, we describe the main behavioral and neural characteristics of CP, and then lay down the building blocks of our proposed model, referring to the existing literature supporting this new framework. We then propose testable predictions and conclude with open questions for future research stemming from this model. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.