Ancestral analysis of a Native American Ecuadorian family with congenital insensitivity to pain with anhidrosis

Abstract

Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by self-mutilating behavior, unexplained fever, inability to sweat and intellectual disability. CIPA pathogenesis is associated with genetic loss-of-function mutations of the NTRK1 gene, which is auto phosphorylated activating intracellular signaling transduction such as cell survival, growth and differentiation. CIPA occurs with an incidence of 1 in 125 million newborns, and only some hundreds of cases have been reported worldwide. Most of cases have been reported in Asian countries. Here, we estimate the ancestral proportions of a family with consanguinity background affected with CIPA, who carries the missense pathogenic mutations rs80356677 (Asp674Tyr) in the kinase domain of NTRK1 and rs324420 (Pro129Thr) in the FAAH gene. The ancestral proportion was calculated through 45 ancestry informative markers (AIMs) and the comparison was done through the Human Genome Diversity Project panel. The resulting allele frequencies in CIPA family indicate a prevalence of the Native American ancestral component with 87.9%, and minor proportion for the European (8.9%) and African (3%) components. In conclusion, the genetic variations expressing CIPA in a Native American Ecuadorian family could have been caused by the insertion of certain genetic characteristics, which have been passed down from common ancestors as consequence of migration towards South America.