Diagnostic and clinical utility of next‐generation sequencing in children born with multiple congenital anomalies in the China neonatal genomes project

Wang, Huijun; Xiao, Fei; Dong, Xinran; Lu, Yulan; Cheng, Guoqiang; Wang, Laishuan; Lü, Wei; Yang, Lin; Chen, Liping; Kang, Wenqing; Li, Long; Pan, Xinnian; Wei, Qiufen; Zhuang, Deyi; Chen, Dongmei; Yin, Zhaoqing; Yang, Ling; Ni, Qi; Liu, Renchao; Li, Gang; Zhang, Ping; Qian, Yanyan; Li, Xu; Peng, Xiaomin; Wang, Yao; Liu, Fang; Wang, Dahui; Li, Hao; Shen, Chun; Qian, Liling; Cao, Yun; Wu, Bingbing; Zhou, Wenhao

doi:10.1002/humu.24170

Cited by 22 publications

(14 citation statements)

References 31 publications

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“…39 Sequencing of individuals with multiple congenital anomalies, particularly those across body systems, has a high likelihood to yield a molecular diagnosis. 40,41 Together, these findings suggest that additional clinical and genetic evaluations of boys with hypospadias may identify subclinical birth defects and improve molecular diagnoses for boys with multiple congenital anomalies.…”

Section: Discussionmentioning

confidence: 94%

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias

et al. 2022

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Key Points Question What is the relative prevalence of congenital heart defects among boys born with hypospadias compared with boys born without hypospadias? Findings In this large multistate birth defects registry cohort study of data from population-based birth defect surveillance programs on all male infants born in 11 US states, boys born with hypospadias were 6 times more likely than boys without hypospadias to have any major congenital heart defect. Meaning This study suggests that screenings for additional birth defects among boys born with hypospadias may be warranted; in addition, molecular studies are needed to uncover the shared etiology of co-occurring defects in different developmental fields.

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Section: Discussionmentioning

confidence: 94%

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias

et al. 2022

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“…DNA fragments were enriched for exome sequences using the IDT xGen Exome Research Panel v2 (Integrated DNA Technologies, Coralville, IA, USA). According to our previous reports, sequencing was performed on NovaSeq 6000 (Illumina, San Diego, USA) according to protocols ( 10 ). The data analysis followed the pipeline established by our team ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay

Zhao

Chen

et al. 2022

Front. Pediatr.

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Craniosynostosis is a premature fusion of cranial sutures, resulting in abnormally shaped skull and brain development disorder. The description of craniosynostosis in patients with BCL11B mutations is rare. Here, we firstly report a 25-month-old Chinese boy with a novel frameshift variant in BCL11B gene. The patient was identified c.2346_2361del by whole-exome sequencing and was confirmed to be de novo by parental Sanger sequencing. This patient presented clinical phenotype of craniosynostosis as well as global developmental delay. He had a small mouth, thin upper lip, arched eyebrows, a long philtrum, midfacial hypoplasia and craniosynostosis. Brain MRI showed brain extracerebral interval and myelination changes, and brain CT with 3D reconstruction showed multi-craniosynostosis. Our study expands the clinical phenotypes of patients with BCL11B gene mutation, and our findings may help guide clinical treatment and family genetic counseling.

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“…The pathogenicity of the variant was defined based on the American College of Medical Genetics and Genomics criteria ( 12 ). Detailed methods can be found in our previous studies ( 13 , 14 ).…”

Section: Methodsmentioning

confidence: 99%

Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes?

Tang

Xiao

et al. 2021

Front. Pediatr.

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Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes.

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Diagnostic and clinical utility of next‐generation sequencing in children born with multiple congenital anomalies in the China neonatal genomes project

Cited by 22 publications

References 31 publications

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias

Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay

Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes?

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