Whole Exome Screening of Newborns

Infant, Newborn Clinical Trial

Official title:

Development of the Technology and Methodology for Generation of the Genetic Passport (Genetic Health Record) of Newborn and Application Thereof to Estimate the Mid and Low Penetrance Hereditary Disorders Frequencies in Russian Population and to Uncover Genetic Factors Determining Severe Monogenic Conditions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05325749
• Other study ID #: Examen
• Status: Recruiting
• Start date: July 10, 2021
• Est. completion date: December 2022

Study information

• Verified date: December 2021
• Source: Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
• Contact: Jekaterina Shubina, PhD
• Phone: +7 926 721-87-17
• Email: jekaterina.shubina[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of the study is to obtain the initial experience of the inclusive genetic screening of newborn.

Two groups of newborns born in RCOGP will be enlisted to the study:

1. newborns without developmental features having no variations according to an inherited diseases screening;

2. newborns showing either phenotypic features or deviations according to MS screening.

The residual volume of the cord blood of all newborns form both groups will be collected and subjected to the whole exome sequencing. The sequencing data will be analyzed in "screening" mode for the first group while for the second group analysis will be performed taking the respective phenotype into account.

The study is planned to cover 7000 newborns in total.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7000
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Group 1 (newborns without features):

Inclusion Criteria:

• Infants born in the RCOGP, showing no development features and with no inherited diseases revealed by common screening

• Informed consent signed by a newborn's representative

Exclusion Criteria:

• Parents refuse to participate

• Parent(s) younger 18 years

• Parent(s) unable to make decisions

• The infant is older 30 d

• Blood cannot be collected from the infant

Group 2 (newborns with phenotypic features)

Inclusion Criteria:

• Infants showing either phenotypic features or deviations according to MS screening

• Informed consent signed by a newborn's representative

Exclusion Criteria:

• Parents refuse to participate

• Parent(s) younger 18 years

• Parent(s) unable to make decisions

• Blood cannot be collected from the infant

• Detailed description of the phenotype is not available

• The infant's exome has been already sequenced

Related Conditions & MeSH terms

• Infant, Newborn

Intervention

Genetic:
• Screening
Whole exome sequencing will be done and all infants will receive a report which will include pathogenic or likely pathogenic variants identified in genes associated with childhood-onset diseases for which specific care or prevention protocols are available. Families signed additional informed consent will receive an advanced report including variants with no care or prevention available, mid or low risk variants, and variants with late onset or those suggesting relatives to undergo screening.
• Family history record
Families enrolled to the study will receive a genetic consult during which a family history will be taken concerning the inherited conditions.

Other:
• Questionnaire survey
Families invited to the study will be asked to undergo a questionnaire survey regarding the reasons to accept or refuse the study, the familiarity of the aims, methods and outcomes of the study as well as the satisfaction.

Genetic:
• Diagnostic
The results of whole exome sequencing will be analysed according to the infant's phenotype in addition the the general screening pipeline
• Selective screening
The results of whole exome sequencing will be analysed according to the data of prenatal ultrasound examination, family history and other available alarming information in addition the the general screening pipeline

Locations

Country	Name	City	State
Russian Federation	Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate the frequency of revealing patients carrying genotype associated with a monogenic disese.	The manifestation of pathogenic or likely pathogenic variants leading to a monogenic disease presenting during early age.; A genotype is considered having risk of developping a monogenic disease in case pathogenic or probably pathogenic variants are detected corresponding to the inheritance model.	3-5 months
Primary	Phenotype-associated variants	Pathogenic, likely pathogenic variants or variants of uncertain significance corresponding to the observed clinical conditions	2 weeks - 2 months
Primary	Motivations for refuse to participate	Questionnaire answers provided by families refused to enroll	1 day
Primary	Acceptance of advanced screening	Questionnaire answers provided by families accepted screening for variants of low penetrance, no care available etc.	1 day
Secondary	Oncological risk	Pathogenic or a likely pathogenic variant causing high risk of developping a cancer	1 day
Secondary	Cardiological risk	Pathogenic or a likely pathogenic variant causing high risk of developping a cardiomyopathy or a sudden cardiac death	1 day
Secondary	Recessive carriers	Inheritance of a pathogenic or a likely pathogenic variant causing to an autosomal recessive disease	1 day