title: Fortuitous detection of a submicroscopic deletion at 1q25 in a girl with Cornelia-de Lange syndrome carrying t(5;13)(p13.1;q12.1) by array-based comparative genomic hybridization.
abstract: We report on a 2-year-old Japanese girl with Cornelia-de Lange syndrome (CdLS) who had mental and growth retardation, together with characteristic facial anomalies and mild extremity malformations. She had a balanced chromosomal translocation, 46,XX,t(5;13)(p13.1;q12.1) de novo. Surprisingly, this was the same translocation that had provided a clue to the identification of a major causative gene for CdLS, NIPBL [Krantz et al., 2004; Tonkin et al., 2004]. Using fluorescence in situ hybridization (FISH), the breakpoint was confirmed to lie within NIPBL at 5p13.1. Furthermore, array-based comparative genomic hybridization (array-CGH) demonstrated a cryptic 1-Mb deletion harboring six known genes at 1q25-q31.1. A FISH analysis of her parents confirmed that the deletion was de novo. Although patients with interstitial deletions at 1q are rare, some of their features were similar to those observed in our patient, indicating that her clinical manifestations are likely to be affected by not only the disruption of NIPBL but also the concomitant microdeletion at 1q25-q31.1. The present case suggests that array-CGH can uncover cryptic genomic aberrations affecting atypical phenotypes even in well-known congenital disorders.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, and Department of Pediatrics, Tokyo Teishin Hospital, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.forename: Masae
authors.initials: M
authors.lastname: Ono
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D002675:Child, Preschool; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D014178:Translocation, Genetic