Molecular Quality Improvement Program

CDC Services
Suzanne Cordovado, Ph.D.
Team Lead, Molecular Quality Improvement Program
Newborn Screening and Molecular Biology Branch,
Division of Laboratory Sciences
Tuesday, 28th June 2011
National Center for Environmental Health
Centers for Disease Control and Prevention
Newborn Screening and Molecular
Biology Branch Organization
Newborn Screening and
Molecular Biology Branch
(6 teams)
Screening Quality
Research Initiative
Biochemical Mass
Molecular Quality
The Newborn Screening
Quality Assurance Program
The only comprehensive quality assurance
program using the dried-blood spots
Laboratory Services Provided by NSQAP
Filter paper evaluation
DBS reference and quality control materials
Proficiency Testing
Internet reporting site for laboratories
Follow-up of False negative results
Training, consultation, network resources
Translation Research Initiative
Assure that the translation of research
methods into routine laboratory tests
for newborn screening leads to
sustainable high-quality testing and
healthier babies worldwide
 Develop new screening methods for specific diseases
 Integrate State Public Health Laboratories into the translation
process through collaborative field studies
 Expand global reach of newborn screening
 Adapt innovative technologies for screening and quality
Ongoing collaboration between the CDC Foundation and NSMBB
Biochemical Mass Spectrometry Laboratory
Mission Statement:
Work with public health partners to develop new mass spectrometrybased assays to detect and monitor metabolic disorders, and enhance
newborn screening laboratory performance through innovative
approaches to biochemical marker detection.
Selected Priorities:
 Develop new methods for the analysis of driedblood for metabolic screening and diagnosis of
selected inborn errors of metabolism
 Pilot program for MS/MS analyte ratios
analysis for metabolic disorders to improve
specificity of existing MS/MS-based newborn
screening assays
Molecular Quality Improvement Program
Work with public health laboratories to detect newborn disorders
with molecular methods, and provide a public health forum to
exchange molecular best practices, quality improvements and
educational resources to enhance laboratory performance.
 Molecular screening brings new and different
technologies into the NBS laboratory creating a need for
newborn screening laboratory resources
 Second tier and primary molecular methods are now
being used by a number of newborn screening
NBS Molecular Testing Status: 2010
36 state labs (denoted in green) offer a molecular test
84% of babies born/year
Molecular Quality Improvement Activities
 Establishment of the NBS Molecular Network
 Implementation of NBS Molecular Assessment Program
 QA research to identify and develop quality molecular
methods for the DBS matrix
 Molecular characterization of quality assurance (QA)
materials (e.g. cystic fibrosis and hemoglobinopathies)
 Translational research to address NBS community
identified needs and QA protocols
Establishment of the NBS Molecular Network
Public health partners working synergistically to
enhance newborn screening with molecular tests
2010 NBS and Genetic Testing Symposium
Facilitate a collaborative
environment for knowledge and
technology transfer between
NBS labs
Assist labs in improving
sensitivity and/or specificity of
detection using primary or
second-tier molecular tests
Collaborate with NBS labs to
anticipate future molecular
assays and needs
NBS Molecular Network Goals
Steering committee is comprised of
NSMBB staff, Public Health partners and
 1st meeting – February 23-24, 2011, Atlanta, GA
 Goal 1: Prioritize disorders to implement molecular
tests to enhance screening
 Goal 2: Identify collaborative projects to fill gaps in
molecular NBS
 Goal 3: Plan strategies to enhance communication,
education and dissemination of best molecular lab
Quality Assurance Research:
Evaluation of DNA Extracted from DBS in NBS Assays
Determine DBS DNA extraction efficiency of commercially
available extraction methods
Test downstream assay performance in NBS laboratories
Cystic fibrosis – InPlex CF (Hologic) and xTAG CF 39 (Luminex)
Galactosemia – in-house GALT assay
Hemoglobinopathies – in-house HBB assay
SCID – in-house TREC assay
State public health partners: California, Massachusetts, New
York, Texas, Washington, and Wisconsin
Quality Assurance Research:
CFTR Inplex Optimization for DNA from DBS
Collaboration with Delaware NBS Laboratory
Determine minimum volume of input DNA
from DBS for InPlex CF assay
 DBS DNA is not routinely quantitated
 Recommended input volume is 5 µl
Results indicate robust genotypes with input
volumes > 2 µl
rcentage of failed samples for which a low probe set signal occurred
Analysis suggests probe sets 3905insT,
2184delA and W1282X fail more frequently
when input DNA volume < 2 µl
Low Probe Set Signals in Failed Samples by Sample Type and
 Samples tested: newborn DBS and NSQAP
Low Probe Set Signals in Failed Samples
Percentage of failed samples for which a low probe set signal occurred
Low Probe Set Signals in Failed S
Mutation Probe Set for which more th
NSQAP failures @ 1 ul (n=9)
NSQAP failures @ 0.5 ul (n=19)
NBS failures @ 1 ul (n=5)
NBS failures @ 0.5 ul (n=20)
Future MQIP Projects
Web-based NBS molecular lab resource center
 Guidelines/troubleshooting/education for molecular NBS assays
 Discussion forum
Implementation of the Molecular Assessment
 Provide quality management guidance and support for molecular testing
in NBS laboratories
 Partnership between MQIP, NBS laboratories and APHL
Research and Development to expand molecular
 Population mutation panels
 Creation of QA materials and services
Future MQIP Projects cont.
Characterization of hemoglobinopathies in PT
samples – Ghanaian Collaboration
 Confirm abnormal hemoglobin gene variants
Expanded CF Repository
 Sustain and expand CF PT repository to include currently
unavailable mutations
 Create DBS QC materials for assay development and validation
Molecular Quality Improvement Program
Team Members
Suzanne Cordovado
Christopher Greene
Laura Hancock
Miyono Hendrix
Stanimila (Mimi) Nikolova
Sean Mochal
Daniel Turner
Team Lead
MAP Coordinator
Web & Research Specialist
Research Specialist
Research Specialist
ORISE Fellow
ORISE Fellow
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
For more information please contact Centers for Disease Control and
1600 Clifton Road NE, Atlanta, GA 30333
Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: [email protected] Web:
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
National Center for Environmental Health
Centers for Disease Control and Prevention

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