MAP3K4 and spina bifida aperta: Interestingly, we had one case with anencephaly and thoracic lumbar spina bifida aperta (the neural tube was closed in cervical region), who carried two missense mutations in the MAP3K4 gene involved in MAPK signaling (MAP3K4: NM_005922: c.877G > A: p.D293N and c.2711C > G: p.T904S)(Fig. 7b).