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

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine100 enrolled

Overview

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

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 Type

OBSERVATIONAL

Enrollment

100

Conditions

Intellectual Disability Multiple Congenital Anomaly Rare Diseases

Interventions

Whole genome sequencingDIAGNOSTIC_TEST

WGS will be performed for the trio

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

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.);

Locations (14)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Number of diagnosed families

Families with rare and undiagnosed pediatric genetic disease will be benefitted by WGS.

Time frame: 1 year

Secondary Outcomes

Numbers of pathogenic variants in different variation types

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.

Time frame: 1 year

Central Contacts

Yu Sun, PhD

CONTACT

+86-25-25076466 sunyu@xinhuamed.com.cn

Xiaomei Luo, Ms

CONTACT

+86-25-25076466 luoxiaomei@xinhuamed.com.cn

Data from ClinicalTrials.gov

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