Intellectual Disability, Multiple Congenital Anomaly, Rare Diseases
Conditions
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
Interventions
DIAGNOSTIC_TESTWhole genome sequencing
WGS will be performed for the trio
Sponsors
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Observational model
FAMILY_BASED
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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.);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of diagnosed families | 1 year | Families with rare and undiagnosed pediatric genetic disease will be benefitted by WGS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactYu Sun, PhD
Backup ContactXiaomei Luo, Ms
Outcome results
None listed