 One study showed evidence that a mutation in the NRTN gene was not enough along to cause onset of the disease, however when coupled with a mutation in the RET gene, disease was present in family members as well as the individual.A more recent study showed NRTN variants present in individuals with Hirschsprung disease.However, RET associated mutations were not found and in one variant, RET phosphorylation levels were reduced, which has the potential to have downstream effects on the proliferation and differentiation of neuronal crests.