Clinical trial NCT03424772: Whole Genome Sequencing in the Detection of Rare Undiagnosed Genetic Diseases in Children in China
Official title: Clinical Collaborative Research of Whole Genome Sequencing in the Detection of Rare Undiagnosed Genetic Diseases in Children in China
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Intellectual Disability
Multiple Congenital Anomaly
Rare Diseases
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2018-02-07
Enrollment: 100
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Undiagnosed Children with intellectual disability/developmental delay and/or multiple congenital abnormalites in China

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

Eligibility criteria: 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.);

Primary outcomes:
measure: Number of diagnosed families
timeFrame: 1 year
Secondary outcomes:
measure: Numbers of pathogenic variants in different variation types
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Children's Hospital, Capital Institute of Pediatrics
state: Beijing
city: Beijing
country: China
facility: Department of Pediatrics, Peking University First Hospital
state: Beijing
city: Nanning
country: China
facility: The Maternal & Child Health Hospital, The Children's Hospital, The Obstetrics & Gynecology Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Changsha
country: China
facility: The Maternal and Child Health Hospital of Hunan Province
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital, Central-south University / Hunan Jiahui genetics hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing maternal and children hospital
state: Jiangsu
city: Shanghai
country: China
facility: Ruijin Hospital affiliated to Shanghai Jiaotong University
state: Shanghai
city: Shanghai
country: China
facility: Children's Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Institute for Pediatric Research
state: Shanghai
city: Shanghai
country: China
facility: Xin Hua Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
state: Shanghai
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
Study officials:
affiliation: Specify Unaffiliated
name: Yongguo Yu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park ST, Kim J. Trends in Next-Generation Sequencing and a New Era for Whole Genome Sequencing. Int Neurourol J. 2016 Nov;20(Suppl 2):S76-83. doi: 10.5213/inj.1632742.371. Epub 2016 Nov 22.