PDF(Pubmed)
Abstract：
Chromosomal aberrations/rearrangements are the most common cause of intellectual disability (ID), developmental delay (DD), and congenital malformations. Traditionally, karyotyping has been the investigation of choice in such cases, with the advantage of being cheap and easily accessible, but with the caveat of the inability to detect copy number variations of sizes less than 5 Mb. Chromosomal microarray can solve this problem, but again the problems of expense and poor availability are major challenges in developing countries. The purpose of this study is to find the utility of multiplex ligation-dependent probe amplification (MLPA) as a middle ground, in a resource-limited setting. We also attempted to establish an optimum cutoff for the de Vries score, to enable physicians to decide between these tests on a case-to-case basis, using only clinical data. A total of 332 children with DD/ID with or without facial dysmorphism and congenital malformations were studied by MLPA probe sets P245. Assessment of clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history was done. We also scored the de Vries scoring for all the patients to find a suitable cutoff for MLPA screening. In our study, the overall detection rate of MLPA was 13.5% (45/332). The majority of patients were DiGeorge\'s syndrome with probe deletion in 22q11.21 in 3.3% (11/332) followed by 15q11.2 del in 3.6% (12/332, split between Angelman\'s and Prader-Willi\'s syndromes). Also, 3.0% (10/332) of patients were positive for Williams-Beuren\'s syndrome 7q11.23, 1.8% (6/332) for Wolf--Hirschhorn\'s syndrome 4p16.3, 1.2% (4/332) for 1p36 deletion, and 1% for each trichorhinophalangeal syndrome type I 8q23.3 duplication syndrome and cri du chat syndrome. The optimum cutoff of de Vries score for MLPA testing in children with ID and/or dysmorphism came out to be 2.5 (rounded off to 3) with a sensitivity of 82.2% and specificity of 66.7%. This is the largest study from India for the detection of chromosomal aberrations using MLPA common microdeletion kit P245. Our study suggests that de Vries score with a cutoff of 3 or more can be used to offer MLPA as the first tier test for patients with unexplained ID, with or without facial dysmorphism and congenital malformations.
摘要：
染色体畸变/重排是智力障碍（ID）的最常见原因，发育迟缓（DD），先天性畸形.传统上,在这种情况下，核型分析一直是研究的选择，具有便宜且易于访问的优势，但需要注意的是，无法检测到大小小于5Mb的拷贝数变化。染色体微阵列可以解决这个问题，但是，费用和可用性差的问题再次成为发展中国家的主要挑战。这项研究的目的是找到多重连接依赖性探针扩增（MLPA）作为中间地带的效用，在资源有限的环境中。我们还试图为deVries得分建立一个最佳截止值，为了使医生能够根据具体情况在这些测试之间做出决定，仅使用临床数据。通过MLPA探针组P245研究了332名患有或没有面部畸形和先天性畸形的DD/ID儿童。评估与出生史有关的临床变量，面部畸形,先天性畸形,家族史已经完成。我们还对所有患者的deVries评分进行了评分，以找到合适的MLPA筛查截止值。在我们的研究中,MLPA的总检出率为13.5%(45/332)。大多数患者为DiGeorge综合征，在22q11.21中探针缺失占3.3％（11/332），其次是15q11.2del占3.6％（12/332，分为Angelman和Prader-Willi综合征）。此外，3.0%(10/332)的患者对Williams-Beuren综合征7q11.23阳性，1.8%(6/332)的患者对Wolf-Hirschhorn综合征4p16.3阳性，1.2%(4/332)的患者对1p36缺失阳性，和1％的每一个三鼻综合征I型8q23.3重复综合征和criduchat综合征。ID和/或畸形儿童MLPA测试的deVries评分的最佳截止值为2.5（四舍五入为3），灵敏度为82.2％，特异性为66.7％。这是印度使用MLPA常见微缺失试剂盒P245检测染色体畸变的最大研究。我们的研究表明，deVries评分的临界值为3或更高，可用于提供MLPA作为无法解释的ID患者的第一层测试，有或没有面部畸形和先天性畸形。
