title: A de novo GLI3 mutation in a patient with acrocallosal syndrome.
abstract: 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.
authors: Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors: Leonie
authors: L
authors: Speksnijder
authors: Titia E
authors: TE
authors: Cohen-Overbeek
authors: Maarten F C M
authors: MF
authors: Knapen
authors: Simone M
authors: SM
authors: Lunshof
authors: A Jeannette M
authors: AJ
authors: Hoogeboom
authors: Ans M
authors: AM
authors: van den Ouwenland
authors: Irenaneus F M
authors: IF
authors: de Coo
authors: Maarten H
authors: MH
authors: Lequin
authors: Hanno J
authors: HJ
authors: Bolz
authors: Carsten
authors: C
authors: Bergmann
authors: Leslie G
authors: LG
authors: Biesecker
authors: Patrick J
authors: PJ
authors: Willems
authors: Marja W
authors: MW
authors: Wessels
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D055673:Acrocallosal Syndrome / Q000175:diagnosis / Q000235:genetics*; D000168:Acrocephalosyndactylia / Q000175:diagnosis / Q000235:genetics*; D019943:Amino Acid Substitution; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007223:Infant; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis; D000074290:Zinc Finger Protein Gli3
chemical_list: C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3