CHRND variant in a paternally inherited esophageal atresia and tracheoesophgageal fistula: Report of a case

BackgroundThe familial occurrence of esophageal atresia and tracheoesophageal fistula (EA-TEF) is very rare and the genetic basis behind the isolated familial cases have not been identified. A male infant born with EA-TEF and his affected father were evaluated with whole genome sequence to define a genetic causative variation in paternally inherited EA-TEF.Case ReportA male infant was born to 29-years-old, gravida 1, para 1 women by normal vaginal delivery. The patient was diagnosed as Type-C EA-TEF. In his family history, his father was also operated for EA-TEF during neonatal period. He had no associated anomaly despite patent foramen ovale. Genomic DNAs were extracted from peripheral blood of the patient and the father. When causative genes responsible for EA-TEF were filtered out, four different variants in NOTCH2, SAMD9, SUPT20H and CHRND were found. Except the variant found in CHRND (NM_000751.2, c.381C>G, p.(Tyr127Ter)), other three variants were not found to be segregated with the father who has EA-TEF also. This nonsense variant was not found in GnomAD database.ConclusionCHRND variant found in both EA-TEF patient and his affected father suggest that CHRND variant might possibly be considered as one of the causative genetic variants in familial isolated EA-TEF patients.

Automated summary

The genetic basis behind the isolated familial cases of esophageal atresia and tracheoesophageal fistula (EA-TEF) is not well understood. In this case report, a male infant born with EA-TEF and his affected father were evaluated using whole genome sequencing to identify a genetic causative variation. Several variants were found, including one in the CHRND gene that was present in both the patient and his father.