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

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Unknown status

CT.gov ID

NCT03424772

Collaborator

(none)

100

Enrollment

Locations

13.4

Anticipated Duration (Months)

7.1

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Intellectual Disability Multiple Congenital Anomaly Rare Diseases	Diagnostic Test: Whole genome sequencing

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

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Family-Based

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 18, 2018

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Patients with unexplained DD/ID 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.	Diagnostic Test: Whole genome sequencing WGS will be performed for the trio

Arm

Intervention/Treatment

Patients with unexplained DD/ID

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.

Diagnostic Test: Whole genome sequencing

WGS will be performed for the trio

Outcome Measures

Primary Outcome Measures

Number of diagnosed families [1 year]
Families with rare and undiagnosed pediatric genetic disease will be benefitted by WGS.

Secondary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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).
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
Families went through at least one of the high throughput technology(WES or CMA) and receive the negative result

Exclusion Criteria:

Intellectual disability caused by pregnancy, perinatal infection, ischemia, and hypoxia and other non-hereditary causes,
Obvious genetic metabolic diseases (such as different types of genetic metabolic diseases, bone disease, fragile X syndrome, etc.);

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking Union Medical College Hospital	Beijing	Beijing	China	100005
2	Children's Hospital, Capital Institute of Pediatrics	Beijing	Beijing	China	100020
3	Department of Pediatrics, Peking University First Hospital	Beijing	Beijing	China	100034
4	The Maternal & Child Health Hospital, The Children's Hospital, The Obstetrics & Gynecology Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi	China	530005
5	The Maternal and Child Health Hospital of Hunan Province	Changsha	Hunan	China	410008
6	Xiangya Hospital, Central-south University / Hunan Jiahui genetics hospital	Changsha	Hunan	China	410008
7	Hunan Children's Hospital	Changsha	Hunan	China	410011
8	Nanjing maternal and children hospital	Nanjing	Jiangsu	China	210004
9	Ruijin Hospital affiliated to Shanghai Jiaotong University	Shanghai	Shanghai	China	200025
10	Children's Hospital of Shanghai	Shanghai	Shanghai	China	200041
11	Shanghai Institute for Pediatric Research	Shanghai	Shanghai	China	200092
12	Xin Hua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200092
13	Shanghai Children's Medical Center	Shanghai	Shanghai	China	201712
14	Wenzhou Central Hospital	Wenzhou	Zhejiang	China	325099