Human Molecular Genetics Advance Access originally published online on February 3, 2009
Human Molecular Genetics 2009 18(8):1377-1383; doi:10.1093/hmg/ddp042
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Identification of familial and de novo microduplications of 22q11.21–q11.23 distal to the 22q11.21 microdeletion syndrome region
1 Signature Genomic Laboratories, LLC, 2820 N. Astor St., Spokane, WA 99207, USA 2 Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA 3 Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA 4 Weisskopf Child Evaluation Center, University of Louisville, Louisville, KY, USA 5 Cheyenne Children's Clinic, Cheyenne, WY, USA 6 Department of Molecular and Human Genetics, Indiana University School of Medicine, Indianapolis, IN, USA 7 Department of Medical Genetics, Carle Clinic, Bloomington, IL, USA 8 Department of Medical Genetics, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA 9 Children's Hospital Central California, Madera, CA, USA 10 Sacred Heart Medical Center, Spokane, WA, USA 11 WWAMI Medical Education Program, Washington State University, Spokane, WA, USA 12 School of Molecular Biosciences, Washington State University, Spokane, WA, USA
* To whom correspondence should be addressed. Tel: +1 5099444219; Fax: +1 5094746839; Email: shaffer{at}signaturegenomics.com
Received September 25, 2008; Revised January 12, 2009; Accepted January 20, 2009
Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21–q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.