Phenotypic spectrum associated with pathogenic mutation in the NRG1 gene in Acadian family

NRG1 is a gene that encodes for a protein that binds to a receptor of the tyrosine kinase family which is essential for the survival of the central nervous system development during embryogenesis. Mutation of the NRG1 gene causes aganglionosis, which leads to Hirschsprung disease. Two brothers of Acadian descent presented with a history of Hirschsprung disease, in association with other anomalies including congenital heart disease, learning difficulties, developmental issues, and hypopigmented hair patch. Molecular analysis in both siblings revealed a heterozygous pathogenic mutation in the NGR1 gene (c.235C>T [p.Arg79*]), that was inherited from an unaffected father. This family expands our knowledge about the phenotypic spectrum associated with pathogenic mutation in the NRG1 gene with intrafamilial variability and the likely reduced penetrance for the phenotypic expression.