Further studies have shown that a V332A mutation in Shh was implicated in a case of solitary median maxillary central incisor syndrome (SMMCI) [41], a novel Shh missense mutation (C to T) in the coding region (resulting in a Val for Ala substitution; A43V) was found in a patient with severe median cleft lip/mandible [42], and a 14-month-old girl with submucous cleft palate was found to harbour a duplication of the chromosome region located near the Shh gene on 7q36 [43], indicating an important role for Shh in human craniofacial development. This evidence concerns the gene SHH and solitary median maxillary central incisor syndrome.