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

Intellectual Disability Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03424772
• Other study ID #: XH-18-001
• Status: Recruiting
• Phase: N/A
• First received: January 30, 2018
• Last updated: February 6, 2018
• Start date: January 18, 2018
• Est. completion date: March 2019

Study information

• Verified date: February 2018
• Source: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: Yu Sun, PhD
• Phone: +86-25-25076466
• Email: sunyu[@]xinhuamed.com.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.);

Related Conditions & MeSH terms

• Abnormalities, Multiple
• Congenital Abnormalities
• Genetic Diseases, Inborn
• Intellectual Disability
• Multiple Congenital Anomaly
• Rare Diseases

Intervention

Diagnostic Test:
• Whole genome sequencing
WGS will be performed for the trio

Locations

Country	Name	City	State
China	Children's Hospital, Capital Institute of Pediatrics	Beijing	Beijing
China	Department of Pediatrics, Peking University First Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Hunan Children's Hospital	Changsha	Hunan
China	The Maternal and Child Health Hospital of Hunan Province	Changsha	Hunan
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	Children's Hospital of Shanghai	Shanghai	Shanghai
China	Ruijin Hospital affiliated to Shanghai Jiaotong University	Shanghai	Shanghai
China	Shanghai Children's Medical Center	Shanghai	Shanghai
China	Shanghai Institute for Pediatric Research	Shanghai	Shanghai
China	Xin Hua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Wenzhou Central Hospital	Wenzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

References & Publications (1)

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. Epub 2016 Nov 22. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of diagnosed families	Families with rare and undiagnosed pediatric genetic disease will be benefitted by WGS.	1 year
Secondary	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.	1 year

External Links

•   Trends in Next-Generation Sequencing and a New Era for Whole Genome Sequencing.