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 of research combining classic genetics and modern genomics. 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 and were also associated with CPs in the cohort study. In another 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.