Human genetics of face recognition: discovery of MCTP2 mutations in humans with face blindness (congenital prosopagnosia).

This article focuses on the identification of mutations in the MCTP2 gene as a genetic basis for congenital prosopagnosia (CP), a selective impairment in face recognition. Through 17 years of research involving a large Chinese family with 18 CP members, linkage analysis localized a CP susceptibility locus to chromosome 15q26.1-26.2, where a private missense mutation (p.I716S) in MCTP2 fully co-segregated with the CP phenotype. Additional rare functional mutations, including a frameshift mutation (p.S80fs), were found in multiple cohorts, with gene-based association analyses supporting a correlation between rare MCTP2 variants and face recognition deficits, particularly in males. Functional magnetic resonance imaging (fMRI) revealed that CP individuals carrying MCTP2 mutations exhibited abnormal neural adaptation responses to repeated facial identities in the right fusiform face area, a brain region critical for face processing. These findings represent the first identification of a gene required for a higher form of human visual social cognition and provide a molecular genetic link to face recognition abilities.