Genetic Analysis of Children With Unexplained Developmental Delay and/or Intellectual Disability by Whole-Exome Sequencing

Xiang, Jingjing; Ding, Yang; Yang, Fei; Gao, Ang; Zhang, Wei; Tang, Hui; Mao, Jun; He, Quanze; Zhang, Qin; Wang, Ting

doi:10.3389/fgene.2021.738561

Cited by 18 publications

(10 citation statements)

References 43 publications

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“…WES has become a primary clinical diagnostic tool for children suffering from developmental delays, intellectual disabilities, respiratory disease [ 10 , 19 ], and more. Recent discussions have highlighted its use in NICU settings and among neonatal populations in China, viewing it from various perspectives [ 2 , 9 , 12 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing as the first-tier test for patients in neonatal intensive care unit: a Chinese single-center study

Zhang,

Cui,

Zhang

et al. 2024

BMC Pediatr

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Background Genetic disorders significantly affect patients in neonatal intensive care units, where establishing a diagnosis can be challenging through routine tests and supplementary examinations. Whole-exome sequencing offers a molecular-based approach for diagnosing genetic disorders. This study aimed to assess the importance of whole-exome sequencing for neonates in intensive care through a retrospective observational study within a Chinese cohort. Methods We gathered data from neonatal patients at Tianjin Children’s Hospital between January 2018 and April 2021. These patients presented with acute illnesses and were suspected of having genetic disorders, which were investigated using whole-exome sequencing. Our retrospective analysis covered clinical data, genetic findings, and the correlation between phenotypes and genetic variations. Results The study included 121 neonates. Disorders affected multiple organs or systems, predominantly the metabolic, neurological, and endocrine systems. The detection rate for whole-exome sequencing was 52.9% (64 out of 121 patients), identifying 84 pathogenic or likely pathogenic genetic variants in 64 neonates. These included 13 copy number variations and 71 single-nucleotide variants. The most frequent inheritance pattern was autosomal recessive (57.8%, 37 out of 64), followed by autosomal dominant (29.7%, 19 out of 64). In total, 40 diseases were identified through whole-exome sequencing. Conclusion This study underscores the value and clinical utility of whole-exome sequencing as a primary diagnostic tool for neonates in intensive care units with suspected genetic disorders. Whole-exome sequencing not only aids in diagnosis but also offers significant benefits to patients and their families by providing clarity in uncertain diagnostic situations.

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Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing as the first-tier test for patients in neonatal intensive care unit: a Chinese single-center study

Zhang,

Cui,

Zhang

et al. 2024

BMC Pediatr

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“…WES has been recommended as a rst-tier clinical diagnostic test for children patients who infected with developmental delay, intellectual disability, and respiratory disease et al [8,11]. But there were few article about the application in NICU in China.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing as the first-tier test for patients in neonatal intensive care unit: A Chinese single-center study

Zhang,

Cui,

Zhang

et al. 2023

Preprint

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Background: Genetic disorders are the part of critical patients in neonatal intensive care unit, it is difficult to establish the diagnosis of pathogenesis via rountine detections and accessory examination. Whole exome sequencing may provide the evidence based on molecular diagnose for genetic disorders. Our aim was to explore the significance of whole exome sequencing for patients in neonatal intensive care unit by the retrospective observational study in a Chinese cohort of neonates. Methods: The neonatal patients were collected in Tianjin Children’s Hospital from January 2018 to April 2021, who had an acute illness and were suspected with genetic disorders performed by whole exome sequencing. We analysed retrospectively the clinical data, genetic findings, and the relationship between phenotype and genetic variation in this study. Results: A total of 121 neonates were enrolled in this study. Multiple organ or system were involved in the current study, mainly in metabolic, neurologic, endocrine system. The overall positive rate of whole exome sequencing was 55.4% (67/121), 94 pathogenic or likely pathogenic genomic variants of were identified in 67 neonates, of which the number of copy number varation and single-nucleotide variant were 20 and 74 respectively. The most common inheritance pattern of them was autosomal recessive, up to the rate of 56.7% (38/67), the second one was autosomal dominant inheritance, accounting for 29.8% (19/67). Up to 40 diseases were diagnosed via whole exome sequencing in this study. Conclusion: Based on the study and the available evidence of this cohort , we strongly recommend and support whole exome sequencing as the first-tier test for patients with suspected genetic disorders in neonatal intensive care unit. Whole exome sequencing demonstrates clinical utility and the significance for patients and their familes in situation of the absence of dignosis.

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“…In a recent study, exome-based single nucleotide variant (SNV) and Indel calling combined with exome-based CNV analysis in ES data from patients with NDD, revealed an overall diagnostic yield of 54.0% (35.1% from SNV/Indel and 18.9% from exome based CNV) [ 54 ]. A similar study explored diagnostic yield in unexplained DD/ID using exome-based exon-level Indel and CNV analysis, and reported an overall diagnostic yield of 58.8% (41.2% from SNV/Indel constitute and 17.6% CNV) [ 55 ].…”

Section: Genetic and Metabolic Investigations In Children With Gdd/idmentioning

confidence: 99%

Evaluation of Individuals with Non-Syndromic Global Developmental Delay and Intellectual Disability

et al. 2023

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Global Developmental Delay (GDD) and Intellectual Disability (ID) are two of the most common presentations encountered by physicians taking care of children. GDD/ID is classified into non-syndromic GDD/ID, where GDD/ID is the sole evident clinical feature, or syndromic GDD/ID, where there are additional clinical features or co-morbidities present. Careful evaluation of children with GDD and ID, starting with detailed history followed by a thorough examination, remain the cornerstone for etiologic diagnosis. However, when initial history and examination fail to identify a probable underlying etiology, further genetic testing is warranted. In recent years, genetic testing has been shown to be the single most important diagnostic modality for clinicians evaluating children with non-syndromic GDD/ID. In this review, we discuss different genetic testing currently available, review common underlying copy-number variants and molecular pathways, explore the recent evidence and recommendations for genetic evaluation and discuss an approach to the diagnosis and management of children with non-syndromic GDD and ID.

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Genetic Analysis of Children With Unexplained Developmental Delay and/or Intellectual Disability by Whole-Exome Sequencing

Cited by 18 publications

References 43 publications

Whole-exome sequencing as the first-tier test for patients in neonatal intensive care unit: a Chinese single-center study

Whole-exome sequencing as the first-tier test for patients in neonatal intensive care unit: a Chinese single-center study

Whole exome sequencing as the first-tier test for patients in neonatal intensive care unit: A Chinese single-center study

Evaluation of Individuals with Non-Syndromic Global Developmental Delay and Intellectual Disability

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