Kumar A, Becker L A, Depinet T W, Haren J M, Kurtz C L, Robin N H, Cassidy S B, Wolff D J, Schwartz S
Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, OH 44106-9959, USA.
Hum Genet. 1998 Aug;103(2):173-8. doi: 10.1007/pl00008706.
To test the hypothesis that the phenotypic abnormalities seen in cases with apparently balanced chromosomal rearrangements are the result of the presence of cryptic deletions or duplications of chromosomal material near the breakpoints, we analyzed three cases with apparently balanced chromosomal rearrangements and phenotypic abnormalities. We characterized the breakpoints in these cases by using microsatellite analysis by polymerase chain reaction and fluorescence in situ hybridization analysis of yeast artificial chromosome clones selected from the breakpoint regions. Molecular characterization of the translocation breakpoint in patient 1 [46,XY,t(2;6)(p22.2;q23.1)] showed the presence of a 4- to 6-Mb cryptic deletion between markers D6S412 and D6S1705 near the 6q23.1 breakpoint. Molecular characterization of the proximal inversion 7q22.1 breakpoint in patient 2 [46,XY,inv(7)(q22.1q32.1)] revealed the presence of a 4-Mb cryptic deletion between D7S651 and D7S515 markers. No deletion or duplication of chromosomal material was found near the breakpoints in patient 3 [46,XX,t(2;6)(q33.1;p12.2)]. Our study suggests that a systematic molecular study of breakpoints should be carried out in cases with apparently balanced chromosomal rearrangements and phenotypic abnormalities, because cryptic deletions near the breakpoints may explain the phenotypic abnormalities in these cases.
在染色体排列明显平衡的病例中所观察到的表型异常是由于断点附近存在染色体物质的隐匿性缺失或重复，我们分析了3例染色体排列明显平衡且有表型异常的病例。我们通过聚合酶链反应的微卫星分析以及对从断点区域选出的酵母人工染色体克隆进行荧光原位杂交分析，来确定这些病例中的断点。对患者1[46,XY,t(2;6)(p22.2;q23.1)]的易位断点进行分子特征分析，结果显示在6q23.1断点附近的标记D6S412和D6S1705之间存在一个4至6兆碱基的隐匿性缺失。对患者2[46,XY,inv(7)(q22.1q32.1)]近端7q22.1倒位断点进行分子特征分析，发现在D7S651和D7S515标记之间存在一个4兆碱基的隐匿性缺失。在患者3[46,XX,t(2;6)(q33.1;p12.2)]的断点附近未发现染色体物质的缺失或重复。我们的研究表明，对于染色体排列明显平衡且有表型异常的病例，应进行断点的系统分子研究，因为断点附近的隐匿性缺失可能解释这些病例中的表型异常。
