Use of medical exome sequencing for identification of underlying genetic defects in <scp>NICU</scp>: Experience in a cohort of 2303 neonates in China

Yang, Lin; Wei, Zejun; Chen, Xiang; Hu, Liyuan; Peng, Xiaomin; Wang, Jin; Lu, Chunmei; Kong, Yanting; Dong, Xinran; Ni, Qi; Lu, Yulan; Wu, Bingbing; Wang, Huijun; Meirelles, Katia; Tian, Xia; Zhang, Jing; Chang, Fengqi; Liu, Liu; Li, Changhua; You, Wesley; Cheng, Guoqiang; Wang, Laishuan; Cao, Yun; Chen, Chao; Fang, Ping; Tang, Sha; Zhou, Wenhao

doi:10.1111/cge.14075

Cited by 24 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was similar to previous positive results reported in China using the identical sequencing approach (approximately 10%). 32 , 33 Nevertheless, it was a lower rate than that of previously reported exome/genome sequencing (ES/GS) participants for causative variants in rare disorders (25–50%). 4 , 11–19 This discrepancy was probably attributed to variations in sample size, inclusive criteria, analytical manner, characteristics of the studied diseases, and the range of genes covered between our cohort and others.…”

Section: Discussionmentioning

confidence: 75%

A Retrospective Analysis of Clinically Focused Exome Sequencing Results of 372 Infants with Suspected Monogenic Disorders in China

An¹,

Lei²,

Liu³

et al. 2023

PGPM

View full text Add to dashboard Cite

Objective The context was designed to optimize the diagnostic utility of clinically focused exome sequencing (CFES) and shorten the diagnostic odyssey among pediatric patients suspected of monogenic disorders (MDs). Methods Here, we retrospectively analyzed the clinical notes of 372 patients from different areas in the Jiangxi province that were referred for a diagnostic CFES and analysis from June 2018 to March 2022 with symptoms suggestive of MDs. In our study, preliminary tests using the proband-only clinical exome sequencing as a cost-effective first-tier diagnostic test for pediatric patients with unidentified MDs, supplemented by family segregation studies for targeted variants when indicated. Results Probands with confirmed diagnostic (CD) or likely diagnostic (LD) genetic influences accounted for 12% of all cases, whereas those with an uncertain diagnosis accounted for 48%. We also found that systemic primary carnitine deficiency (CDSP) ( SLC22A5 gene) and phenylketonuria ( PAH gene) were relatively more prevalent, and these patients with CDSP had the most frequent c.1400C > G variant (p.S467C) and c.51C > G variant (p. F17L) in this study. In addition, statistical analysis revealed that the estimates of diagnostic yields varied across certain phenotypic features of patients, and patients with specific phenotypic traits tended to benefit more from CFES. Conclusion The CFES may be a first-line genetic test for diagnosing young children with suspected genetic conditions, as it validates the identification of molecular genetics alterations and facilitates comprehensive medical management. Moreover, we found that infants exhibiting metabolism/homeostasis abnormalities, craniofacial /otolaryngology/ ophthalmologic abnormalities, and/or the integument were significantly more likely to receive a genetic diagnosis via CFES than infants without such features. However, due to the current study’s low diagnostic yield and inherent limitations, high-quality clinical studies with larger sample sizes are still needed to provide more likely results and confirm our findings.

show abstract

Section: Discussionmentioning

confidence: 75%

A Retrospective Analysis of Clinically Focused Exome Sequencing Results of 372 Infants with Suspected Monogenic Disorders in China

An¹,

Lei²,

Liu³

et al. 2023

PGPM

View full text Add to dashboard Cite

show abstract

“…This control data set was from the same clinical settings with detailed clinical and genetic information that was published previously. 24 The clinical information was obtained from electronic medical records and telephone call follow-ups.…”

Section: Methodsmentioning

confidence: 99%

“…As a control, the non-ART group was randomly sampled at a ratio of 1:3 from the CNGP data set between August 1, 2016, and December 31, 2018. This control data set was from the same clinical settings with detailed clinical and genetic information that was published previously . The clinical information was obtained from electronic medical records and telephone call follow-ups.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Genetic Profiles of Neonates in Intensive Care Units Conceived With or Without Assisted Reproductive Technology

Huang

Xiao

et al. 2023

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceA growing number of children are conceived with assisted reproductive technology (ART). However, there is a lack of studies systematically analyzing the genetic landscape of live-born children conceived through ART who need intensive care in the neonatal period.ObjectiveTo investigate the incidence and type of molecular defects among neonates conceived through ART who are in intensive care units (NICUs) with suspected genetic conditions.Design, Setting, and ParticipantsThis was a cross-sectional study using data from the China Neonatal Genomes Project, a multicenter national neonatal genome data set managed by the Children’s Hospital of Fudan University. All participants were from level III and IV NICUs and included 535 neonates conceived through ART with suspected genetic conditions, with data collected between August 1, 2016, and December 31, 2021, and 1316 naturally conceived neonates with suspected genetic conditions in the same clinical settings, with data collected between August 1, 2016, and December 31, 2018. The data were analyzed between September 2021 and January 2023.ExposuresWhole-exome sequencing or target clinical exome sequencing with pathogenic or likely pathogenic single-nucleotide variant (SNV) and copy number variation (CNV) detection was performed for each individual.Main Outcomes and MeasuresThe primary outcome was the molecular diagnostic yield, mode of inheritance, spectrum of genetic events, and incidence of de novo variants.ResultsA total of 535 neonates conceived through ART (319 boys [59.6%]) and 1316 naturally conceived neonates (772 boys [58.7%]) were included. A genetic diagnosis was established for 54 patients conceived through ART (10.1%), including 34 patients with SNVs (63.0%) and 20 with CNVs (37.0%). In the non-ART group, 174 patients (13.2%) received a genetic diagnosis, including 120 patients with SNVs (69.0%) and 54 with CNVs (31.0%). The overall diagnostic yield was comparable between the ART group and the naturally conceived neonates (10.1% vs 13.2%; odds ratio [OR], 0.74; 95% CI, 0.53-1.02), as was the proportion of SNVs (63.0% vs 69.0%; OR, 0.68; 95% CI, 0.46-1.00) and CNVs (37.0% vs 31.0%; OR, 0.91; 95% CI, 0.54-1.53) detected by sequencing. Furthermore, the proportions of de novo variants in the ART group and the non-ART group were similar (75.9% [41 of 54] vs 64.4% [112 of 174]; OR, 0.89; 95% CI, 0.62-1.30).Conclusions and RelevanceThis cross-sectional study of neonates in NICUs suggests that the overall genetic diagnostic yield and the incidence of de novo variants were similar between live-born neonates conceived through ART and naturally conceived neonates in the same settings.

show abstract

“…Three patients who enrolled in the China Neonatal Genomes Project (CNGP) (10) and were diagnosed with GAMOS3 between August 2016 and December 2021 were included in this study. Patients' parents or legal guardians agreed and signed informed consent for DNA sequencing.…”

Section: Patient Selection and Phenotypingmentioning

confidence: 99%

Galloway–Mowat Syndrome Type 3 Caused by OSGEP Gene Variants: A Case Report and Literature Review

Huang

Yang

et al. 2022

Front. Pediatr.

Self Cite

View full text Add to dashboard Cite

BackgroundGalloway–Mowat syndrome type 3 (GAMOS3) is an extremely rare and severe autosomal-recessive disease characterized by early-onset nephrotic syndrome (NS), microcephaly and neurological impairment. Reported GAMOS cases have gradually increased since pathogenic OSGEP variants were identified as the aetiology in 2017.MethodsUsing whole-exome sequencing and a data analysis process established by Children's Hospital of Fudan University, the clinical and molecular features of 3 infants with OSGEP mutations were summarized. Literature regarding the clinical features of GAMOS3 caused by OSGEP variants was reviewed.ResultsThirty-seven individuals (3 from this study) from 34 families were included. Twenty-two different OSGEP variants were identified. The c.740G>A (p.Arg247Gln) variant in OSGEP was detected in 15 families (44%), all from Asia. Most affected individuals (including patients I and II in this study) showed a typical phenotype, including microcephaly (92%) with brain anomalies (97%), developmental delay (81%), congenital NS (54%), and craniofacial (94%) and skeletal dysmorphism (84%). Renal manifestations varied from proteinuria (94%, median onset = 1.5 months) to NS (83%) and end-stage renal disease (48%, 11 months) during follow-up. Patients with congenital NS had a lower survival probability (median survival time = 3 months) than those without congenital NS (78 months) (P < 0.01, log-rank test).ConclusionGAMOS3 is a progressive renal-neurological syndrome with a poor prognosis, especially with congenital NS. Microcephaly with dysmorphic features are vital clues to further evaluate renal impairment and brain anomalies. Timely molecular diagnosis is crucial for clinical decision-making, appropriate treatment and genetic counselling.

show abstract

Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China

Cited by 24 publications

References 34 publications

A Retrospective Analysis of Clinically Focused Exome Sequencing Results of 372 Infants with Suspected Monogenic Disorders in China

A Retrospective Analysis of Clinically Focused Exome Sequencing Results of 372 Infants with Suspected Monogenic Disorders in China

Comparison of Genetic Profiles of Neonates in Intensive Care Units Conceived With or Without Assisted Reproductive Technology

Galloway–Mowat Syndrome Type 3 Caused by OSGEP Gene Variants: A Case Report and Literature Review

Contact Info

Product

Resources

About