Cheng S D, Spinner N B, Zackai E H, Knoll J H
Division of Genetics, Children's Hospital, Boston, MA 02115.
Am J Hum Genet. 1994 Oct;55(4):753-9.
We have studied the inverted duplicated chromosomes 15 (inv dup(15)) from 11 individuals--7 with severe mental retardation and seizures, 3 with a normal phenotype, and 1 with Prader-Willi syndrome (PWS). Through a combination of FISH and quantitative DNA analyses, three different molecular sizes of inv dup(15) were identified. The smallest inv dup(15) was positive only for the centromeric locus D15Z1 (type 1); the next size was positive for D15Z1 and D15S18 (type 2); and the largest inv dup(15) was positive for two additional copies of loci extending from D15Z1 and D15S18 through D15S12 (type 3). Type 1 or type 2 was observed in the three normal individuals and the PWS patient. Type 3 was observed in all seven individuals with mental retardation and seizures but without PWS or Angelman Syndrome (AS). The PWS patient, in addition to being mosaic for a small inv dup(15), demonstrated at D15S63 a methylation pattern consistent with maternal uniparental inheritance of the normal chromosomes 15. The results from this study show (a) two additional copies of proximal 15q loci, D15S9 through D15S12, in mentally retarded patients with an inv dup(15) but without AS or PWS and (b) no additional copies of these loci in patients with a normal phenotype or with PWS.
我们研究了11名个体的倒位重复15号染色体（inv dup(15)）——7名患有严重智力迟钝和癫痫，3名表型正常，1名患有普拉德-威利综合征（PWS）。通过荧光原位杂交（FISH）和定量DNA分析相结合的方法，鉴定出了三种不同分子大小的inv dup(15)。最小的inv dup(15)仅着丝粒位点D15Z1呈阳性（1型）；次大的inv dup(15) D15Z1和D15S18呈阳性（2型）；最大的inv dup(15)从D15Z1和D15S18延伸至D15S12的位点有另外两个拷贝呈阳性（3型）。在3名正常个体和PWS患者中观察到1型或2型。在所有7名患有智力迟钝和癫痫但无PWS或天使综合征（AS）的个体中观察到3型。该PWS患者除了存在小的inv dup(15)嵌合体之外，在D15S63处显示出与正常15号染色体的母系单亲遗传一致的甲基化模式。本研究结果表明：（a）在患有inv dup(15)但无AS或PWS的智力迟钝患者中，15号染色体长臂近端D15S9至D15S12有另外两个拷贝；（b）在表型正常或患有PWS的患者中没有这些位点的额外拷贝。
