Whole Exome Screening of Newborns

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

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.

Study Overview

• Status: Recruiting
• Conditions: Infant, Newborn
• Intervention / Treatment: Genetic: Screening; Genetic: Family history record; Other: Questionnaire survey; Genetic: Diagnostic; Genetic: Selective screening

• Study Type: Observational
• Enrollment (Anticipated): 7000

Contacts and Locations

• Study Contact: Name: Jekaterina Shubina, PhD; Phone Number: +7 926 721-87-17; Email: jekaterina.shubina@gmail.com
• Study Contact Backup: Name: Andrey A Bystritskiy, PhD; Phone Number: +7 903 722-10-34; Email: andrey.bystritskiy@yandex.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117997
    • Recruiting
    • Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
    • Contact: Elena A Gorodnova, PhD; Phone Number: +7 (495) 531-44-44; Email: e_gorodnova@oparina4.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All infants born in the RCOGP or under treatment in an ICU departmetn of the RCOGP

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
unaffected; newborns without developmental features having no variations according to an inherited diseases screening;	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.; Genetic: 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.
affected; newborns showing either phenotypic features or deviations according to MS screening	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.; Genetic: 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
refused families; parents refused to enroll their newborns to the study	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.
unaffected born prematurely; newborns without specific developmental features having no variations according to an inherited diseases screening, born before term	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.; Genetic: 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: 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
unaffected wirh family history; newborns without developmental features having no variations according to an inherited diseases screening but with affected relative(s)	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.; Genetic: 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: 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
unaffected wirh prenatal phenotype; newborns without developmental features at birth and on, having no variations according to an inherited diseases screening which had been observed to show signs of developmental features during prenatal ultrasound examination	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.; Genetic: 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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Phenotype-associated variants	Pathogenic, likely pathogenic variants or variants of uncertain significance corresponding to the observed clinical conditions	2 weeks - 2 months
Motivations for refuse to participate	Questionnaire answers provided by families refused to enroll	1 day
Acceptance of advanced screening	Questionnaire answers provided by families accepted screening for variants of low penetrance, no care available etc.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oncological risk	Pathogenic or a likely pathogenic variant causing high risk of developping a cancer	1 day
Cardiological risk	Pathogenic or a likely pathogenic variant causing high risk of developping a cardiomyopathy or a sudden cardiac death	1 day
Recessive carriers	Inheritance of a pathogenic or a likely pathogenic variant causing to an autosomal recessive disease	1 day

Collaborators and Investigators

• Sponsor: Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
• Investigators: Study Director: Dmitriy Y Trofimov, DSc, Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: newborn; genetic screening; whole exome
• Other Study ID Numbers: Examen

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No