title: Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10,362 consecutive cases.
abstract: Somatic chromosomal mosaicism arising from post-zygotic errors is known to cause several well-defined genetic syndromes as well as contribute to phenotypic variation in diseases. However, somatic mosaicism is often under-diagnosed due to challenges in detection. We evaluated 10,362 patients with a custom-designed, exon-targeted whole-genome oligonucleotide array and detected somatic mosaicism in a total of 57 cases (0.55%). The mosaicism was characterized and confirmed by fluorescence in situ hybridization (FISH) and/or chromosome analysis. Different categories of abnormal cell lines were detected: (1) aneuploidy, including sex chromosome abnormalities and isochromosomes (22 cases), (2) ring or marker chromosomes (12 cases), (3) single deletion/duplication copy number variations (CNVs) (11 cases), (4) multiple deletion/duplication CNVs (5 cases), (5) exonic CNVs (4 cases), and (6) unbalanced translocations (3 cases). Levels of mosaicism calculated based on the array data were in good concordance with those observed by FISH (10-93%). Of the 14 cases evaluated concurrently by chromosome analysis, mosaicism was detected solely by the array in 4 cases (29%). In summary, our exon-targeted array further expands the diagnostic capability of high-resolution array comparative genomic hybridization in detecting mosaicism for cytogenetic abnormalities as well as small CNVs in disease-causing genes.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Pham
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Shaw
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Pursley
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hixson
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Srirangan
authors.initials: S
authors.lastname: Sampath
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Roney
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Allina Medical Laboratories, Minneapolis, MN, USA.
authors.forename: Sung-Hae L
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Texas Children's Hospital, Houston, TX, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Lalani
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Texas Children's Hospital, Houston, TX, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bacino
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Texas Children's Hospital, Houston, TX, USA [3] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sau-Wai
authors.initials: SW
authors.lastname: Cheung
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005091:Exons; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009030:Mosaicism; D009154:Mutation; D055815:Young Adult