一个2p25与12p13隐匿性重排家系的遗传学诊断及基因分析  

Genetic diagnosis and analysis of related genes for a pedigree with 2p25 and 12p13 cryptic rearrangements

作　　者：涂向东[1] 曾健[1] 丛学文[1] 严爱贞[1] 林宇翔[1] 张晓[1] 丘丽萍[1] 周游[1] 兰风华[1] 

机构地区：[1]南京军区福州总医院全军检验医学研究所实验科,福州350025

出　　处：《中华医学遗传学杂志》2014年第4期444-448,共5页Chinese Journal of Medical Genetics

基　　金：南京军区医学科技创新资助项目（11MA106）

摘　　要：目的对1例智力低下与精神发育异常的患儿及其双亲进行染色体畸变分析。方法应用染色体G显带分析、亚端粒区多重连接依赖探针扩增（multiplex ligation-dependent probe amplification，MLPA）、荧光原位杂交（fluorescence in situ hybridization，FISH）及单核苷酸多态性芯片（single nucleotide polymorphisms array，SNP-array）等技术分析该家系染色体及相关基因的异常。结果染色体G显带检测显示患儿染色体核型为46，XX，母亲核型为46，XX，add（12）（p13），父亲核型为46，XY。亚端粒区MLPA检测提示患儿2p25区ACP1基因拷贝数减少，12p13区SLC6A12、KDM5A基因拷贝数增加，父母MLPA未见异常。SNP-array显示患儿12p13．33-p12．3区15．142Mb重复，造成SLC6A12等9个基因重复，2p25．3区3．194Mb杂合性缺失，造成sNTG2等11个基因缺失。FISH分析提示患儿46，XX，ish，der（2），t（2；12）（p25；p13）mat，即2p25部分单体和12p13部分三体，患儿母亲46，XX，isht（2；12）（p25；p13），为染色体隐匿性平衡易位携带者。SNTG2、MYTIL基因缺失，SLC6A12基因重复可能与患儿精神发育异常、智力低下有关。结论MLPA、FISH和SNP-Array等技术联合应用可以更好地从基因组水平诊断隐匿性染色体重排。Objective To analyze chromosome aberration in a child with mental retardation and abnormalities and its parents. Methods Chromosome G banding, multiplex ligation-dependent probe amplification, fluorescence in situ hybridization and single nucleotide polymorphisms array were employed for analysis. Results Karyotype analysis revealed that the child was 46, XX and the father was 46, XY, while the mother was 46,XX, add （12）（p13）. Subtelomeric region analysis with MLPA displayed that the child has reduced ACP1 gene copy number in 2p25 region and increased SLC6A12, KDM5A gene copy numbers in 12pll region. SNP-array has fine mapped the duplication to 12p13. 33-p12. 3, a 15. 142 Mb region, and a deletion to 2p25.3 for 3. 194 Mb, which resulted in duplication of 9 genes including SLC6A12 as well as deletion of 11 genes including SNTG2, respectively. FISH analysis revealed that the child was 46, XX,ish,der（2）,t（2;12）（p25;p13）mat, or partial monosomy 2p25 and partial trisomy 12p13. In addition, the mother was a carrier with cryptic balanced translocation chromosome, 46, XX, isht （ 2 ; 12） （p25 ; p1 3）. Mental abnormalities and retardation of the child may be attributed to heterozygous deletion of SNTG2, MYTIL genes and duplication of SLC6A12 gene. Conclusion Combined use of MLPA, FISH and SNP- array can facilitate accurate diagnosis of cryptic rearrangement at genomic level.

关 键 词：隐匿性重排 多重连接依赖探针扩增 单核苷酸多态性芯片 荧光原位杂交 

分 类 号：R394[医药卫生—医学遗传学]