Genome wide array-CGH and qPCR analysis for the identification of genome defects in Williams' syndrome patients in Saudi Arabia.
Genome wide array-CGH and qPCR analysis for the identification of genome defects in Williams' syndrome patients in Saudi Arabia.
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DOI：
10.1186/s13039-016-0266-4
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发表时间：
2016
影响因子：
1.3
通讯作者：
AlQahtani M
中科院分区：
文献类型：
--
作者：
Hussein IR;Magbooli A;Huwait E;Chaudhary A;Bader R;Gari M;Ashgan F;Alquaiti M;Abuzenadah A;AlQahtani M
Williams-Beuren综合征（WBS）是一种罕见的神经发育障碍，其特征在于畸形特征、心血管缺陷、认知缺陷和发育迟缓。WBS是由7号染色体的节段性非整倍性引起的，这是由于染色体7q11.23长臂处的连续基因的杂合缺失造成的。我们的目的是应用阵列CGH技术检测疑似WBS患者的拷贝数变异，并确定染色体7q11.23缺失片段的大小与表型的相关性。该研究包括24名临时诊断为WBS的CEGMR患者和8名父母。对患者进行常规细胞遗传学（G显带）分析、分子细胞遗传学（荧光原位杂交）、基于阵列的比较基因组杂交（阵列-CGH）和定量真实的时间PCR（qPCR）技术。核型分析未发现缺失，但有1例18、19号染色体不平衡易位，核型为45，XX，der（19）t（18;19）（q11.1;p13.3）-18。FISH技术检测到10/24例患者染色体7q11.23微缺失。阵列CGH和qPCR证实了所有样本中的缺失，并可以在3名患者和2名父母中检测到7q11.23的重复。此外，阵列CGH和qPCR技术都可以准确地检测缺失的大小。3例未显示7q11.23缺失的患者通过阵列CGH诊断为chr9p13.1-p11.2、chr18p11.32-p11.21和chr1p36.13缺失。FISH和阵列-CGH都是诊断WBS的可靠方法;然而，阵列-CGH具有检测基因组缺失/重复的优势，而这些缺失/重复无法通过常规细胞遗传学技术检测。阵列CGH和qPCR可用于检测缺失大小和预测中断的基因及其对疾病表型的影响。染色体7q11.23上缺失基因的大小和功能的影响还需要进一步的研究。ISRCTN ISRCTN 73824458。MOCY-D-16-00041R1。2014年9月28日注册。已登记的逆行。
Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder characterized by dysmorphic features, cardiovascular defects, cognitive deficits and developmental delay. WBS is caused by a segmental aneuploidy of chromosome 7 due to heterozygous deletion of contiguous genes at the long arm of chromosome 7q11.23. We aimed to apply array-CGH technique for the detection of copy number variants in suspected WBS patients and to determine the size of the deleted segment at chromosome 7q11.23 in correlation with the phenotype. The study included 24 patients referred to the CEGMR with the provisional diagnosis of WBS and 8 parents. The patients were subjected to conventional Cytogenetic (G-banding) analysis, Molecular Cytogenetic (Fluorescent In-Situ Hybridization), array-based Comparative Genomic Hybridization (array-CGH) and quantitative Real time PCR (qPCR) Techniques. No deletions were detected by Karyotyping, however, one patient showed unbalanced translocation between chromosome 18 and 19, the karyotype was 45,XX, der(19) t(18;19)(q11.1;p13.3)-18. FISH technique could detect microdeletion in chromosome 7q11.23 in 10/24 patients. Array-CGH and qPCR confirmed the deletion in all samples, and could detect duplication of 7q11.23 in three patients and two parents. Furthermore, the size of the deletion could be detected accurately by both array-CGH and qPCR techniques. Three patients not showing the 7q11.23 deletion were diagnosed by array-CGH to have deletion in chr9p13.1-p11.2, chr18p11.32-p11.21 and chr1p36.13. Both FISH and array-CGH are reliable methods for the diagnosis of WBS; however, array-CGH has the advantage of detection of genome deletions/ duplications that cannot otherwise be detected by conventional cytogenetic techniques. Array-CGH and qPCR are useful for detection of deletion sizes and prediction of the interrupted genes and their impact on the disease phenotype. Further investigations are needed for studying the impact of deletion sizes and function of the deleted genes on chromosome 7q11.23. ISRCTN ISRCTN73824458. MOCY-D-16-00041R1. Registered 28 September 2014. Retrospectively registered.