11q24-q25缺失2例临床表型及文献复习

目的 应用全基因组微阵列芯片平台，对临床发现的多发性畸形患儿进行全基因组拷贝数变异（CNVs）的检测，并寻找基因型与临床表型的关系。方法 采用cytogenetic whole genome芯片筛查全基因组CNVs，针对发现的CNVs进行分析，参照国际基因组CNVs多态性数据库除外正常人群多态性CNVs。结合本研究2例与已报道的Jacobsen综合征(JBS)患儿的临床表型进行比较。结果 2例患儿SNP芯片分析为11q24-q25缺失（7.5和5.6 Mb），均为末端的非单纯性缺失，例1存在12号染色体短臂的较大片段重复（11.5 Mb），例2存在 11号染色体短臂的大片段重复（32.5 Mb）。2例共同缺失的部分均为JBS的关键区段，但临床表型与已报道的JBS患儿有所区别。2例均表现为头面部畸形、心血管系统异常和头颅影像学异常，均未发现血液系统异常。例1还表现为隐睾，例2表现为脾肿大。结论 对临床上难以诊断的多发性畸形可采用全基因组CNVs检测，以帮助明确诊断，对于丰富这一区段临床表型信息具有重要意义，尤其针对罕见疾病，更多的相似报道的后续出现，才能使建立表型-基因型关联性成为可能。

Genotype and phenotype correlations for the deletion of 11q24.2-q25: 2 cases report and literature review

Objective To screen for genomic copy number variants (CNVs) in two independent neonates with multiple congenital malformations using Affymetrix 2.7 M chip, and to identify possible pathologic CNVs and establish the genotype-phenotype correlation. Methods Genomic CNVs were detected in the 2 individuals by using Affymetrix cytogenetic whole genome 2. 7 M array. Rare CNVs with potential clinical significance were selected of which deletion segments' size was larger than 50 kb and duplication segments' size larger than 200 kb based on the analysis of ChAs software, without false positive CNVs and segments of normal population. The identified CNVs with region over 2.5 Mb were selected and further analyzed with related published literatures. Results ① Both two included patients displayed facial dysmorphisms, patent ductus arteriosus, and abnormal finding of MRI. Additionally, cryptorchism in case 1 and splenomegaly in case 2 were reported. ② 4 CNVs of which length was from 5.6-32.5 Mb were identified in 2 neonates, including a 7.5 Mb deletion on 11q24.2-q25 and a 11.4 Mb duplication on 12p13.33-p13.2 in case 1, a 5.5 Mb deletion on 11q24.3-q25 and a 32.5 Mb duplication on 11p13-p15.5 in case 2. ③ The overlapping deletion region of these 2 patients was 11q24-q25. Terminal deletions of the long arm of chromosome 11 caused a haploinsufficiency disorder (Jacobsen syndrome, JBS). Conclusions The study established the methodology to discover whole genome CNVs in identifying complex chromosome rearrangement, allowing an early diagnosis of affected individuals to be made especially neonates without characteristic symptoms. Here, our findings contribute to the refinement of the genotype-phenotype correlations for JBS.