Kehrer Martin, Singer Sylke, Grasshoff Ute, Schäferhoff Karin, Bonin Michael, Riess Olaf, Schöning Martin, Tzschach Andreas
Institute of Human Genetics, University of Tuebingen, and University Children's Hospital, Tuebingen, Germany.
Am J Med Genet A. 2013 Jun;161A(6):1409-13. doi: 10.1002/ajmg.a.35877. Epub 2013 Apr 23.
Deletions of chromosome band 12q24.33 are rare. We report on a 17-year-old male patient with intellectual disability but no major malformations or dysmorphic features in whom a de novo interstitial 660 kb deletion in 12q24.33 was detected by SNP array analysis. This deletion was secondary to a translocation t(12;14)(q24.3;q13)dn that also led to a small deletion in 14q21.1 and a small duplication in 2p23.1. The deletion overlaps with two previously published larger deletions in patients who suffered from intellectual disability, obesity, and polycystic kidney disease, indicating that haploinsufficiency of one or several of the genes in the deleted interval of the patient reported here causes intellectual deficits, but not obesity or renal problems. The 14 RefSeq genes that are harbored by this deletion include P2RX2, which had previously been proposed as a candidate gene for intellectual disability. Thus, the patient reported here broadens our knowledge of the phenotypic consequences of deletions in 12q24.33 and facilitates genotype-phenotype correlations for chromosome aberrations of this region.
12q24.33染色体带的缺失很罕见。我们报告了一名17岁男性患者,他有智力障碍,但无主要畸形或畸形特征,通过单核苷酸多态性(SNP)阵列分析检测到其12q24.33存在一个新生的660kb间质性缺失。该缺失继发于一个t(12;14)(q24.3;q13)dn易位,该易位还导致14q21.1出现一个小的缺失以及2p23.1出现一个小的重复。此缺失与之前报道的两名患有智力障碍、肥胖和多囊肾病患者的两个更大的缺失区域重叠,这表明本文所报道患者缺失区间内一个或几个基因的单倍剂量不足导致智力缺陷,但不导致肥胖或肾脏问题。该缺失区域包含的14个RefSeq基因中包括P2RX2,该基因之前曾被提议作为智力障碍的候选基因。因此,本文所报道的患者拓宽了我们对12q24.33缺失的表型后果的认识,并促进了该区域染色体畸变的基因型-表型相关性研究。