title: Identification of a recurrent microdeletion at 17q23.1q23.2 flanked by segmental duplications associated with heart defects and limb abnormalities.
abstract: Segmental duplications, which comprise approximately 5%-10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are approximately 2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is approximately 2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome.
authors.affiliation: Signature Genomic Laboratories, Spokane, WA 99207, USA. ballif@signaturegenomics.com
authors.forename: Blake C
authors.initials: BC
authors.lastname: Ballif
authors.forename: Aaron
authors.initials: A
authors.lastname: Theisen
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Traylor
authors.forename: Julie
authors.initials: J
authors.lastname: Gastier-Foster
authors.forename: Devon Lamb
authors.initials: DL
authors.lastname: Thrush
authors.forename: Caroline
authors.initials: C
authors.lastname: Astbury
authors.forename: Dennis
authors.initials: D
authors.lastname: Bartholomew
authors.forename: Kim L
authors.initials: KL
authors.lastname: McBride
authors.forename: Robert E
authors.initials: RE
authors.lastname: Pyatt
authors.forename: Kate
authors.initials: K
authors.lastname: Shane
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Smith
authors.forename: Valerie
authors.initials: V
authors.lastname: Banks
authors.forename: William B
authors.initials: WB
authors.lastname: Gallentine
authors.forename: Pamela
authors.initials: P
authors.lastname: Brock
authors.forename: M Katharine
authors.initials: MK
authors.lastname: Rudd
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Adam
authors.forename: Julia A
authors.initials: JA
authors.lastname: Keene
authors.forename: John A
authors.initials: JA
authors.lastname: Phillips
authors.forename: Jean P
authors.initials: JP
authors.lastname: Pfotenhauer
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Gowans
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Bejjani
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019465:Craniofacial Abnormalities / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011995:Recombination, Genetic; D056916:Segmental Duplications, Genomic; D013577:Syndrome; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C491193:TBX4 protein, human