Abstract
Ulnar–mammary syndrome (UMS) is a rare autosomal-dominant disorder caused by mutations in TBX3. The condition is characterized by hypoplasia or aplasia of upper limbs on the ulnar side, mammary glands and nipples, and of apocrine glands in both sexes (MIM #181450). We report on a girl presenting with an UMS like phenotype, a dysmorphic facies, and mental retardation. Mutation analysis of TBX3 and G-banded chromosome analysis from lymphocytes were performed. We used microarray-based comparative genomic hybridization (array CGH) to investigate the patient's genomic DNA for submicroscopic aberrations. No mutation of the TBX3 gene was detected in our patient and chromosome analysis revealed a normal female karyotype (46,XX). Hybridization of a whole-genome tiling path array consisting of more than 36 000 BAC clones revealed an interstitial 1.28 Mb deletion within chromosomal band 12q24.21. The deleted region encompasses one known gene, TBX3. The deletion and haploinsufficiency of TBX3 was confirmed by fluorescence in situ hybridization using BAC clones representing the deletion on the BAC array. To our knowledge, this is the first description of TBX3 haploinsufficiency caused by a genomic deletion in a patient with UMS. We suggest that the UMS phenotype in conjunction with the characteristic facial changes and mental retardation observed in our patient is owing to the deletion of TBX3 and the involvement of neighbouring genes.
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Acknowledgements
We thank Fabienne Trotier and Karen Stout-Weider for their excellent technical assistance in the array CGH and FISH experiments. We are also thankful to the patient and her family for their collaboration in this study. Additionally, we thank the BACPAC Resources Centre for providing the DNA of the human 32k Re-array set, the COST B19 Action for the clones of the subtelomeric set, the Mapping Core and Map Finishing groups of the Wellcome Trust Sanger Institute for initial clone supply and verification of the 1 Mb array and Claus Hultschig for spotting the arrays. The group of Mike Bamshad (Department of Pediatrics, Eccles Institute of Human Genetics, University of Utah) performed the TBX3 mutation analysis. This project was supported by the European Fund for Regional Development. The authors declare to have no competing interests.
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Klopocki, E., Neumann, L., Tönnies, H. et al. Ulnar–mammary syndrome with dysmorphic facies and mental retardation caused by a novel 1.28 Mb deletion encompassing the TBX3 gene. Eur J Hum Genet 14, 1274–1279 (2006). https://doi.org/10.1038/sj.ejhg.5201696
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DOI: https://doi.org/10.1038/sj.ejhg.5201696
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