Klopocki Eva, Neumann Luitgard M, Tönnies Holger, Ropers Hans-Hilger, Mundlos Stefan, Ullmann Reinhard
Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Eur J Hum Genet. 2006 Dec;14(12):1274-9. doi: 10.1038/sj.ejhg.5201696. Epub 2006 Aug 9.
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.
尺骨-乳腺综合征（UMS）是一种由TBX3基因突变引起的罕见常染色体显性疾病。该病的特征是双侧上肢尺侧、乳腺和乳头以及顶泌汗腺发育不全或缺失（MIM #181450）。我们报告了一名表现出类似UMS表型、面容畸形和智力发育迟缓的女孩。对其进行了TBX3突变分析及淋巴细胞G显带染色体分析。我们使用基于微阵列的比较基因组杂交技术（阵列CGH）来检测患者基因组DNA中的亚显微畸变。在我们的患者中未检测到TBX3基因的突变，染色体分析显示为正常女性核型（46,XX）。由超过36000个BAC克隆组成的全基因组平铺路径阵列杂交显示在染色体带12q24.21内存在一个1.28 Mb的间质性缺失。缺失区域包含一个已知基因TBX3。使用代表BAC阵列上缺失的BAC克隆进行荧光原位杂交证实了TBX3的缺失和单倍剂量不足。据我们所知，这是首次描述由基因组缺失导致TBX3单倍剂量不足引起的UMS患者。我们认为，我们患者中观察到的UMS表型以及特征性面部改变和智力发育迟缓是由于TBX3的缺失以及邻近基因的受累。
