Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities
| Autor: | Aaron Theisen, Dennis Bartholomew, Kim L. McBride, Wendy E. Smith, Jean P. Pfotenhauer, Caroline Astbury, Pawel Stankiewicz, Lisa G. Shaffer, Julia A. Keene, William Gallentine, John A. Phillips, Blake C. Ballif, M. Katharine Rudd, Kate P. Shane, Pamela L. Brock, Bassem A. Bejjani, Robert E. Pyatt, Ryan N. Traylor, Valerie Banks, Jill A. Rosenfeld, Margaret P Adam, Julie M. Gastier-Foster, Devon Lamb Thrush, Gordon C. Gowans |
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| Rok vydání: | 2010 |
| Předmět: |
Heart Defects
Congenital Male Microcephaly Adolescent Developmental Disabilities Limb Deformities Congenital Non-allelic homologous recombination Biology Craniofacial Abnormalities Segmental Duplications Genomic Report Gene duplication Genetics medicine Humans Genetics(clinical) In Situ Hybridization Fluorescence Genetics (clinical) Oligonucleotide Array Sequence Analysis Segmental duplication Recombination Genetic Comparative Genomic Hybridization Breakpoint Infant Chromosome Syndrome medicine.disease Phenotype Child Preschool Speech delay Female Chromosome Deletion medicine.symptom T-Box Domain Proteins Chromosomes Human Pair 17 Comparative genomic hybridization |
| Zdroj: | The American Journal of Human Genetics. 86:454-461 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2010.01.038 |
| Popis: | 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 of98% 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. |
| Databáze: | OpenAIRE |
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