Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay

Liu, Yi; Lv, Yuqiang; Zarrei, Mehdi; Dong, Rui; Yang, Xiaomeng; Higginbotham, Edward J; Li, Yue; Zhao, Dongmei; Song, Fengling; Yang, Yali; Zhang, Haiyan; Wang, Ying; Scherer, Stephen W.; Gai, Zhongtao

doi:10.1038/s41525-021-00271-z

Cited by 9 publications

(7 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our diagnostic yield (37.18%) is quite high compared to the estimated 15–20% yield of CMA methods, albeit these estimates are often based on studies where selection criteria were rather broad and CMA resolution was relatively low [ 2 ]. Our diagnostic yield is comparable to several studies with smaller patient groups and/or similarly strict selection criteria [ 5 – 15 ].…”

Section: Discussionsupporting

confidence: 79%

Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort

et al. 2022

View full text Add to dashboard Cite

Background Neurodevelopmental disorders are genetically heterogeneous pediatric conditions. The first tier diagnostic method for uncovering copy number variations (CNVs), one of the most common genetic etiologies in affected individuals, is chromosomal microarray (CMA). However, this methodology is not yet a routine molecular cytogenetic test in many parts of the world, including Hungary. Here we report clinical and genetic data of the first, relatively large Hungarian cohort of patients whose genetic testing included CMA. Methods Clinical data were retrospectively collected for 78 children who were analyzed using various CMA platforms. Phenotypes of patients with disease-causing variants were compared to patients with negative results using the chi squared/Fisher exact tests. Results A total of 30 pathogenic CNVs were identified in 29 patients (37.2%). Postnatal growth delay (p = 0.05564), pectus excavatum (p = 0.07484), brain imaging abnormalities (p = 0.07848), global developmental delay (p = 0.08070) and macrocephaly (p = 0.08919) were more likely to be associated with disease-causing CNVs. Conclusion Our results allow phenotypic expansion of 14q11.2 microdeletions encompassing SUPT16H and CHD8 genes. Variants of unknown significance (n = 24) were found in 17 patients. We provide detailed phenotypic and genetic data of these individuals to facilitate future classification efforts, and spotlight two patients with potentially pathogenic alterations. Our results contribute to unraveling the diagnostic value of rare CNVs.

show abstract

Section: Discussionsupporting

confidence: 79%

Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort

et al. 2022

View full text Add to dashboard Cite

show abstract

“…We found a diagnostic rate of only CMA analysis as 21% presenting 8 pathogenic/likely pathogenic CNVs. In the previous studies including CMA analysis, CNVs were found in the range of 5-35% of the patients, depending on the DD/ID patient selection criteria and classification of detected variants [Miller et al, 2010;Gürkan et al, 2020;Liu et al, 2022]. In our study, we found that the diagnosis was mostly made by NGS methods.…”

Section: Discussionmentioning

confidence: 46%

Clinical and Genetic Characteristics of Patients with Unexplained Intellectual Disability/Developmental Delay without Epilepsy

Çelebi¹,

Aydin²,

Bolat³

et al. 2023

Mol Syndromol

View full text Add to dashboard Cite

Introduction: Global developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD) are mainly evaluated under the neurodevelopmental disorder framework. In this study, we aimed to determine the genetic diagnosis yield using step-by-step genetic analysis in 38 patients with unexplained ID/DD and/or ASD. Methods: In 38 cases (27 male, 11 female) with unexplained ID/DD and/or ASD, chromosomal microarray (CMA) analysis, clinical exome sequencing (CES), and whole-exome sequencing (WES) analysis were applied, respectively. Results: We found a diagnostic rate of only CMA analysis as 21% (8/38) presenting 8 pathogenic and likely pathogenic CNVs. The rate of patients diagnosed with CES/WES methods was 32.2% (10/31). When all pathogenic and likely pathogenic variants were evaluated, the diagnosis rate was 44.7% (17/38). A dual diagnosis was obtained in a case with 16p11.2 microduplication and de novo SNV. We identified eight novel variants: TUBA1A (c.787C>G), TMEM63A (c.334-2A>G), YY1AP1 (c.2051_2052del), ABCA13 (c.12064C>T), ABCA13 (c.13187G>A), USP9X (c.1189T>C), ANKRD17 (c.328_330dup), and GRIA4 (c.17G>A). Conclusion: We present diagnostic rates of a complementary approach to genetic analysis (CMA, CES, and WES). The combined use of genetic analysis methods in unexplained ID/DD and/or ASD cases has contributed significantly to diagnosis rates. Also, we present detailed clinical characteristics to improve genotype-phenotype correlation in the literature for rare and novel variants.

show abstract

“…28,29) Table 3 summarizes the recent studies that highlighted the genetic significance of assessing individuals with GDD/ID and NDDs. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]…”

Section: Genetic Testingmentioning

confidence: 99%

Comprehensive evaluation of the child with global developmental delays or intellectual disability

Aldosari,

Aldosari

2024

Clin Exp Pediatr

View full text Add to dashboard Cite

Global developmental delay (GDD) and intellectual disability (ID) are relatively common neurodevelopmental disorders that significantly impact affected children, their families, and society.The etiology of GDD/ID is notably diverse, encompassing both genetic and acquired factors. Although the precise cause of most GDD/ID cases remains unclear, an estimated half of all cases can be attributed to genetic factors. Thus, a detailed medical history and comprehensive physical examination remain pivotal for guiding diagnostic investigations into the underlying causes of GDD/ID. Advancements in genetic testing have supplanted traditional methods such as karyotyping and fluorescence in situ hybridization with chromosomal microarrays, which are now the primary genetic tests for children with idiopathic GDD/ID. Moreover, the evaluation of Fragile X and Rett syndrome should be an integral component of initial diagnostic assessments. In recent years, whole-exome sequencing and wholegenome sequencing have emerged as important diagnostic tools for evaluating children with GDD/ID and have substantially enhanced the diagnostic yield rates. Gene therapy has emerged as a promising avenue and is poised to become a cornerstone in addressing various genetic developmental and epilepsy disorders. Early intervention facilitated by a proficient multidisciplinary team can markedly enhance the prognosis and outcomes of GDD/ID, particularly when parents or caregivers are actively engaged in the interventional process. This review discusses risk factors and common underlying causes, explores recent evidence and recommendations for genetic evaluation, and offers management strategies for children with GDD/ID.

show abstract

Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay

Cited by 9 publications

References 53 publications

Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort

Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort

Clinical and Genetic Characteristics of Patients with Unexplained Intellectual Disability/Developmental Delay without Epilepsy

Comprehensive evaluation of the child with global developmental delays or intellectual disability

Contact Info

Product

Resources

About