The Gene Dosage Changes of TPTE and BAGE2 and Breakpoint Analysis in Robertsonian Down syndrome
Date Issued
2007
Date
2007
Author(s)
Shaw, Sheng-Wen
DOI
en-US
Abstract
Down syndrome (DS) is the most common single known cause of intellectual disability. Only 4% of DS is Robertsonian translocation (ROB) from acrocentric chromosome rearrangement including chromosome 13, 14, 15, 21 and 22. There are some possible mechanisms of formation of the translocation. Union following breakages in both short arms results in a chromosome with two centromeres. Chromosome 21 is the only acrocentric chromosome that has known genes in short arm. The aim of this study was to define the possible breakage area in 21p when ROB occurs. We prospectively and consecutively collected 10 cases ROB DS from 3 medical centers. Of the 10 DS children, 6 were de novo (60%) and 4 were inheritance (40%). There were 4 der(21q;21q), 4 der(14q;21q), 1 der(13q;21q), and 1 der(21q;22q). The origin of the extra chromosome 21q was maternal in 5 of 6 de novo ROB and was paternal in one case. All of the four der(21q;21q) ROB DS were isochromosome. 10K array comparative genomic hybridization (CGH) was applied to 10 cases that showed the whole long arm amplification in chromosome 21. There was no microscopic nor subtelomeric deletion/duplication in other chromosomes. The result of gene dosage change by real-time quantitative polymerase chain reaction (PCR) was compatible with 244K array CGH in one case. We further used real-time PCR to detect the copy number of TPTE and BAGE2 that located in 21p11, SAMSN1 in 21q11. The ratio of copy number in 21p:21q was 1:3 in der(21q;21q), 2:3 in der(13q;21q), der(14q;21q), and der(21q;22q). Our preliminary results demonstrated breakpoint of chromosome 21 involving ROB might be between BAGE2 and centromere, located from 10.1 Mb to 12.3 Mb.
Subjects
羅伯遜轉位
唐氏症
TPTE
BAGE2
Robertsonian translocation
Down syndrome
Type
other