All authors have no conflicts of interest.
Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype
Article first published online: 7 AUG 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 83, Issue 4, pages 345–351, April 2013
How to Cite
Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype, , , , .
- Issue published online: 12 MAR 2013
- Article first published online: 7 AUG 2012
- Accepted manuscript online: 9 JUL 2012 08:45AM EST
- Manuscript Revised: 29 JUN 2012
- Manuscript Accepted: 29 JUN 2012
- Manuscript Received: 5 APR 2012
- 15q13.3 microdeletion;
- array CGH;
- chromosomal microarray;
- incomplete penetrance;
- variable expressivity
The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion.