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

Shanghai Jiao Tong University

Status: Unknown

Conditions: Multiple Congenital Anomaly; Rare Diseases; Intellectual Disability

Treatments: Diagnostic Test: Whole genome sequencing

Study type: Observational

Funder types: Other

Identifiers

NCT03424772

XH-18-001

Details and patient eligibility

About

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

Full 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

Enrollment: 100 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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.);

Trial design

100 participants in 1 patient group

Patients with unexplained DD/ID

Description:

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.

Treatment:

Diagnostic Test: Whole genome sequencing