Whole Genome Sequencing in the Detection of Rare Undiagnosed Genetic Diseases in Children in China

• Conditions: Rare Diseases; Intellectual Disability; Multiple Congenital Anomaly
• Interventions: Diagnostic Test: Whole genome sequencing

• Registration Number: NCT03424772
• Lead Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary

To assess the indications and diagnostic efficiency of whole genome sequencing (WGS) in pediatric patients with unexplained intellectual disability/developmental delay, multiple congenital abnormalities and other rare and undiagnosed diseases

Detailed Description

This project will recruit 100 rare, undiagnosed pediatric genetic disease families (core families: patients, patients' parents, immediate family members such as brothers and sisters, all of them can be enrolled whether they have disease or not, so generally 3, for a few cases 4 or 5) all over the country. The expert team will review the clinical materials, the molecular team will review the experimental process, and the bioinformatics team will review the chip, the analysis of whole exome sequencing data and screen the samples all over the country;

Whole-genome sequencing of 100 rare, undiagnosed pediatric genetic disease families (Illumina NovaSeq High-throughput Sequencer);

The study will provide preliminarily performance data on the comparison of whole exome data and whole genome data. In addition, it will generate the Chinese Consensus on Clinical Applications of Whole-genome sequencing in the Diagnosis of Birth Defects and Undiagnosed Rare Genetic Diseases in Children based on the statistical analysis of clinical phenotype and genotype association, which could guide the clinical application of pediatrics, laboratory testing and reporting.

Construction of the Chinese detection genome database of genetic disease

Study Timeline

• Study Start: 2018-01-18
• Study First Submitted: 2018-01-30
• Status Verified: 2018-02
• Study First Submitted QC: 2018-02-05
• Last Update Submitted: 2018-02-06
• Study First Posted: 2018-02-07
• Last Update Posted: 2018-02-08
• Primary Completion: 2018-12
• Study Completion: 2019-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Intelligence tests results of less than 40 (patients <3 years old using the Gesell Developmental Scale for screening; patients of 3-6 years old using Little Wechsler Intelligence Scale for screening; patients >6 years old using Old Wechsler Intelligence Scale for screening).
2. Neurodevelopmental defects can be expressed as mental retardation, motor development retardation, language delay, epilepsy, etc. May have or not have Multiple congenital abnormalities, families with more than one affected patient will be enrolled priority
3. Families went through at least one of the high throughput technology(WES or CMA) and receive the negative result

Exclusion Criteria

1. Intellectual disability caused by pregnancy, perinatal infection, ischemia, and hypoxia and other non-hereditary causes,
2. Obvious genetic metabolic diseases (such as different types of genetic metabolic diseases, bone disease, fragile X syndrome, etc.);

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with unexplained DD/ID	Whole genome sequencing	Whole genome sequencing will be performed on pediatric patients with unexplained developmental delay(DD)/intellectual disability(ID), multiple congenital abnormalities and other rare and undiagnosed diseases.

Primary Outcome Measures

Name	Time	Method
Number of diagnosed families	1 year	Families with rare and undiagnosed pediatric genetic disease will be benefitted by WGS.

Secondary Outcome Measures

Name	Time	Method
Numbers of pathogenic variants in different variation types	1 year	WGS would have the potential to detect different types of genetic alterations, such as structure variations, point mutation, small insertion/deletion, trinucleotide repeat, etc. Some types could not be identified by exome sequencing and chromosomal microarray. The numbers of the pathogenic variants in these types will be calculated to examine the benefit of WGS.

Trial Locations

Locations (14)

Children's Hospital, Capital Institute of Pediatrics; 🇨🇳 Beijing, Beijing, China

Wenzhou Central Hospital; 🇨🇳 Wenzhou, Zhejiang, China

Shanghai Institute for Pediatric Research; 🇨🇳 Shanghai, Shanghai, China

Hunan Children's Hospital; 🇨🇳 Changsha, Hunan, China

Department of Pediatrics, Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Xin Hua Hospital, Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China

The Maternal and Child Health Hospital of Hunan Province; 🇨🇳 Changsha, Hunan, China

Shanghai Children's Medical Center; 🇨🇳 Shanghai, Shanghai, China

Children's Hospital of Shanghai; 🇨🇳 Shanghai, Shanghai, China

Xiangya Hospital, Central-south University / Hunan Jiahui genetics hospital; 🇨🇳 Changsha, Hunan, China

Nanjing maternal and children hospital; 🇨🇳 Nanjing, Jiangsu, China

The Maternal & Child Health Hospital, The Children's Hospital, The Obstetrics & Gynecology Hospital of Guangxi Zhuang Autonomous Region; 🇨🇳 Nanning, Guangxi, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

Ruijin Hospital affiliated to Shanghai Jiaotong University; 🇨🇳 Shanghai, Shanghai, China