Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome

Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, f...

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Published in:American journal of medical genetics 2003-12, Vol.123A (3), p.236-242
Main Authors: Johnston, Jennifer J., Olivos-Glander, Isabelle, Turner, Joyce, Aleck, Kyrieckos, Bird, Lynne M., Mehta, Lakshmi, Schimke, R. Neil, Heilstedt, Heidi, Spence, J. Edward, Blancato, Jan, Biesecker, Leslie G.
Format: Article
Language:English
Subjects:
Abnormalities, Multiple - genetics
Abnormalities, Multiple - pathology
acrocallosal
Agenesis of Corpus Callosum
Base Sequence
Biological and medical sciences
Chromosome aberrations
Chromosome Deletion
Chromosomes, Human, Pair 7 - genetics
Cognition Disorders - pathology
Craniofacial Abnormalities
Diagnosis, Differential
DNA Mutational Analysis
DNA-Binding Proteins - genetics
Female
GCPS
Gene Deletion
Genotype
GLI3
Humans
Hypertelorism - pathology
In Situ Hybridization, Fluorescence
Intellectual Disability - pathology
Karyotyping
Kruppel-Like Transcription Factors
Male
Medical genetics
Medical sciences
Nerve Tissue Proteins
Phenotype
Polydactyly - pathology
Syndrome
Transcription Factors - genetics
Zinc Finger Protein Gli3
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Summary:Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes. © 2003 Wiley‐Liss, Inc.
ISSN:1552-4825
0148-7299
1552-4833
1096-8628
DOI:10.1002/ajmg.a.20318