De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models
- 1Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK
- 2Oxford Craniofacial Reconstruction Unit, Woodstock Road, Oxford OX2 6HE, UK
- Correspondence to: Mr G C M Black, Department of Clinical Genetics, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK; gblack{at}man.ac.uk
- Accepted 21 June 2002
- Revised 14 June 2002
Abstract
Acrocallosal syndrome (ACS) is characterised by postaxial polydactyly, hallux duplication, macrocephaly, and absence of the corpus callosum, usually with severe developmental delay. The condition overlaps with Greig cephalopolysyndactyly syndrome (GCPS), an autosomal dominant disorder that results from mutations in the GLI3 gene. Here we report a child with agenesis of the corpus callosum and severe retardation, both cardinal features of ACS and rare in GCPS, who has a mutation in GLI3.
Since others have excluded GLI3 in ACS, we suggest that ACS may represent a heterogeneous group of disorders that, in some cases, may result from a mutation in GLI3 and represent a severe, allelic form of GCPS. The finding is important for counselling families with suspected ACS.
