Genomic analysis of five chromosome 7p deletion patients with Greig cephalopolysyndactyly syndrome (GCPS)

• Published in: European journal of medical genetics 2006-07, Vol.49 (4), p.338-345
• Main Authors: Schwarzbraun, Thomas, Windpassinger, Christian, Ofner, Lisa, Vincent, John B., Cheung, Joseph, Scherer, Stephen W., Wagner, Klaus, Kroisel, Peter M., Petek, Erwin
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Biological and medical sciences; CGS; Chromosome Deletion; Chromosomes, Human, Pair 7; Classical genetics, quantitative genetics, hybrids; Craniofacial Abnormalities - genetics; FISH analysis; Fundamental and applied biological sciences. Psychology; GCPS; General aspects. Genetic counseling; Genetic Techniques; Genetics of eukaryotes. Biological and molecular evolution; Genome; GLI3; Glucokinase - genetics; Greig cephalopolysyndactyly syndrome; Human; Humans; Kruppel-Like Transcription Factors - genetics; Limb Deformities, Congenital - genetics; Medical genetics; Medical sciences; Microdeletion; Microsatellite Repeats; Molecular and cellular biology; Mutation screening; Nerve Tissue Proteins - genetics; PGAM2; Phenotype–genotype correlation; Polymorphic marker analysis; Syndrome; Zinc Finger Protein Gli3
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2005.10.133

Chromosomal deletions on chromosome 7p are associated with Greig cephalopolysyndactyly syndrome (GCPS, OMIM 175700) a syndrome affecting the development of the skull, face, and limbs. We have compared data from molecular cytogenetic and genetic analyses with clinical symptoms from five previously published GCPS deletion patients, including a pair of monozygotic twins. The genomic DNA of the probands and their parents, as well as the DNA from monoallelic cell lines of two patients, was analyzed using microsatellite markers. In some cases (e.g. where the microsatellite studies were uninformative) we also used fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BAC) probes. The fine mapping results of the deletions and genomic data from chromosome 7, were compared to the clinical symptoms. Common breakpoint sequences or mutation hotspots were not observed. Mutation screening for PGAM2, which is responsible for a form of myopathy with recessive inheritance, was performed in all patients. Loss of heterozygosity for known genes with dominant inheritance, such as the glucokinase gene ( GCK), which, when mutated or haploinsufficient, is responsible for maturity-onset diabetes of the young, type II (MODY2, OMIM 125851), was identified and included in a genetic counseling of the patients' families.