Acrocallosal syndrome is characterized by postaxial polydactyly, macrocephaly, agenesis of the corpus callosum, and severe developmental delay. In a few patients with this disorder, a mutation in the KIF7 gene has been reported, which was associated with impaired GLI3 processing and dysregulaton of GLI3 transcription factors. A single patient with acrocallosal syndrome and a de novo p.Ala934Pro mutation in GLI3 has been reported, whereas diverse and numerous GLI3 mutations have also been described in syndromes with overlapping clinical manifestations, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, trigonocephaly with craniosynostosis and polydactyly, oral-facial-digital syndrome, and non-syndromic polydactyly. Here, we describe a second patient with acrocallosal syndrome, who has a de novo, novel c.2786T>C mutation in GLI3, which predicts p.Leu929Pro. This mutation is in the same domain as the mutation in the previously reported patient. These data confirm that mutations in GLI3 are a cause of the acrocallosal phenotype.

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doi.org/10.1002/ajmg.a.35874, hdl.handle.net/1765/68880
American Journal of Medical Genetics. Part A
Department of Clinical Genetics

Speksnijder, L, Cohen-Overbeek, T.E, Knapen, M.F.C.M, Lunshof, S, Hoogeboom, A.J.M, van den Ouwenland, A.M, … Wessels, M.W. (2013). A de novo GLI3 mutation in a patient with acrocallosal syndrome. American Journal of Medical Genetics. Part A, 161(6), 1394–1400. doi:10.1002/ajmg.a.35874