Whole exome sequencing reveals rare variants linked to congenital pouch colon

Importance: Anorectal malformations (ARM) are individually common but Congenital Pouch Colon (CPC), a rare anorectal anomaly causes a dilated pouch in the genitourinary tract.Objective: In this work, we attempted to identify de novo heterozygous missense variants and further discovered variants of unknown significance (VUS) which could provide insights into CPC manifestation and its etiology.Design: From whole exome sequencing (WES) performed earlier, the trio exomes were analysed from those who were admitted in J.K. Lon Hospital, SMS Medical College, Jaipur, India between 2011-2017.Setting: The proband exomes were compared with the unaffected sibling/family members and we sought to ask whether any variants of significant interest are associated with the CPC manifestation.Participants: The WES data from a total of 64 samples including 16 affected neonates with their parents and unaffected siblings were used for the study. Although all samples had unaffected sibling samples and data, we restricted our pool of analyses to all probands (11 male and 5 female) and unaffected parents/siblings.Main outcome: We have earlier attempted to understand the genetic makeup of CPC and identified genes responsible for the disease using WES. We examined the role of rare allelic variation associated with CPC in a 16 proband/parent trio family comparing the mutations to that of their unaffected parents/siblings.Results: Our study across 16 probands revealed extremely rare variants, viz. TAF1B, MUC5B and FRG1.Conclusions and Relevance: The variants were further validated for revealing disease-causing mutations associated with CPC and genitourinary diseases which could close the gaps of surgery by bringing intervention in therapies.