罗伯逊易位型唐氏综合征中TPTE和BAGE2的基因剂量变化及断点分析

Gene dosage change of TPTE and BAGE2 and breakpoint analysis in Robertsonian Down syndrome.

作者信息

Shaw Sheng-Wen, Chen Chih-Ping, Cheng Po-Jen, Wang Tzu-Hao, Hou Jia-Woei, Lin Cheng-Tao, Chang Shuenn-Dhy, Hwa Hsiao-Lin, Lin Ju-Li, Chao An-Shine, Soong Yung-Kuei, Hsieh Fon-Jou

机构信息

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, 333, Taiwan.

Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

J Hum Genet. 2008;53(2):136-143. doi: 10.1007/s10038-007-0229-z. Epub 2007 Dec 12.

DOI:10.1007/s10038-007-0229-z

PMID:18074101

Abstract

Only 4% of Down syndrome (DS) cases have a Robertsonian translocation (ROB). The aim of this study was to define the possible breakage area in 21p where ROB occurs. We prospectively and consecutively collected ten cases ROB DS from three medical centers. Of the ten DS children, six were de novo (60%), and four were due to paternal or maternal inheritance (40%). They consisted of four der(21q;21q), four der(14q;21q), one der(13q;21q), and one der(21q;22q). The origin of the extra chromosome 21q was maternal in five of six de novo ROB and paternal in one case. All four der(21;21) ROB DS were an isochromosome. The result of gene dosage change by real-time quantitative polymerase chain reaction (PCR) was compatible with array-comparative genomic hybridization in one case. We further used real-time PCR to detect the copy number of TPTE and BAGE2 located on 21p11 and SAMSN1 on 21q11. The ratio of copy number in 21p:21q was 1:3 in der(21q;21q) but 2:3 in der(13q;21q), der(14q;21q), and der(21q;22q). Our preliminary results demonstrated the critical breakpoint of chromosome 21 involving ROB might lie between BAGE2 and the centromere, located from 10.1 to 12.3 Mb.

摘要

仅有4%的唐氏综合征（DS）病例存在罗伯逊易位（ROB）。本研究的目的是确定发生ROB时21号染色体短臂（21p）上可能的断裂区域。我们前瞻性且连续地从三个医疗中心收集了10例ROB型DS病例。在这10名DS患儿中，6例为新发（60%），4例为父源或母源遗传（40%）。它们包括4例der(21q;21q)、4例der(14q;21q)、1例der(13q;21q)和1例der(21q;22q)。6例新发ROB病例中有5例额外的21号染色体长臂（21q）起源于母亲，1例起源于父亲。所有4例der(21;21)型ROB DS均为等臂染色体。1例实时定量聚合酶链反应（PCR）检测基因剂量变化的结果与阵列比较基因组杂交结果相符。我们进一步使用实时PCR检测位于21p11的TPTE和BAGE2以及位于21q11的SAMSN1的拷贝数。在der(21q;21q)中，21p与21q的拷贝数之比为1:3，但在der(13q;21q)、der(14q;21q)和der(21q;22q)中为2:3。我们的初步结果表明，涉及ROB的21号染色体关键断点可能位于BAGE2和着丝粒之间，位置在10.1至12.3 Mb之间。