A missense mutation in EBF2 was segregated with imperforate anus in a family across three generations

Abstract

The etiology of imperforate anus, a major phenotype of anorectal malformation (ARM), is still unknown and not a single gene has been reported to be associated with it. We studied a Korean family with six affected members with imperforate anus across three generations by whole exome sequencing and identified a missense mutation in the EBF2 gene (c.215C > T; p.Ala72Val). This mutation is completely segregated with the disease phenotype in the family and is evolutionarily highly conserved among diverse vertebrates. Also, this mutation was predicted to be functionally damaging. These results support that missense mutation in the EBF2 c.215C > T (p.Ala72Val) is very likely to contribute to the pathogenesis of ARM in this family.

Associated anomalies in cases with anorectal anomalies

“…Three genes have been identified that cause syndromic forms of ARA when mutated: SALL1 in Townes–Brocks syndrome (Kohlhase, Wischermann, Reichenbach, Froster, & Engel, ), HLXB9 in Currarino syndrome (Belloni et al, ), and GLI3 in Pallister–Hall syndrome (Böse, Grotewold, & Ruther, ). Kim et al () reported that a missense mutation in EBF2 was segregated with imperforate anus in a family across three generations. EBF proteins interact with important regulators of development, including Hedgehog and BMP signaling (El‐Magd, Allen, McGonnell, Otto, & Patel, ).…”