Srivastava Priyanka, Kaur Parminder, Daniel Roshan, Chaudhry Chakshu, Kaur Anit, Seth Saurabh, Kumari Divya, Kaur Anupriya, Panigrahi Inusha
Genetic Metabolic Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
J Pediatr Genet. 2022 Oct 10;13(2):81-89. doi: 10.1055/s-0042-1757194. eCollection 2024 Jun.
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.
染色体畸变/重排是智力障碍（ID）、发育迟缓（DD）和先天性畸形最常见的原因。传统上，核型分析一直是此类病例的首选检查方法，其优点是价格便宜且易于获得，但缺点是无法检测小于5 Mb的拷贝数变异。染色体微阵列可以解决这个问题，但费用高昂和可及性差的问题在发展中国家仍然是重大挑战。本研究的目的是在资源有限的环境中寻找多重连接依赖探针扩增（MLPA）作为折衷方法的实用性。我们还试图确定德弗里斯评分的最佳临界值，以便医生仅根据临床数据逐案决定这些检查方法的选择。我们使用MLPA探针集P245对总共332例有或无面部畸形和先天性畸形的DD/ID儿童进行了研究。对有关出生史、面部畸形、先天性畸形和家族史的临床变量进行了评估。我们还对所有患者进行了德弗里斯评分，以找到适合MLPA筛查的临界值。在我们的研究中，MLPA的总体检出率为13.5%（45/332）。大多数患者是22q11.21区域探针缺失的迪乔治综合征，占3.3%（第11/332），其次是15q11.2缺失，占3.6%（12/332，安吉尔曼综合征和普拉德-威利综合征各占一部分）。此外，3.0%（10/332）的患者7q11.23区域威廉姆斯-贝伦综合征呈阳性，1.8%（6/332）的患者4p16.3区域沃夫-赫希霍恩综合征呈阳性，1.2%（4/332）的患者1p36缺失呈阳性，I型毛发鼻指综合征8q23.3重复综合征和猫叫综合征各占1%。ID和/或畸形儿童MLPA检测的德弗里斯评分最佳临界值为2.5（四舍五入为3），敏感性为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规模研究。我们的研究表明，临界值为3或更高的德弗里斯评分可用于将MLPA作为不明原因ID患者（有或无面部畸形和先天性畸形）的一线检测方法。
