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NASA NTRS2011

Framework for Integrating Science Data Processing Algorithms Into Process Control Systems

A software framework called PCS Task Wrapper is responsible for standardizing the setup, process initiation, execution, and file management tasks surrounding the execution of science data algorithms, which are referred to by NASA as Product Generation Executives (PGEs). PGEs codify a scientific algorithm, some step in the overall scientific process involved in a mission science workflow. The PCS Task Wrapper provides a stable operating environment to the underlying PGE during its execution lifecycle. If the PGE requires a file, or metadata regarding the file, the PCS Task Wrapper is responsible for delivering that information to the PGE in a manner that meets its requirements. If the PGE requires knowledge of upstream or downstream PGEs in a sequence of executions, that information is also made available. Finally, if information regarding disk space, or node information such as CPU availability, etc., is required, the PCS Task Wrapper provides this information to the underlying PGE. After this information is collected, the PGE is executed, and its output Product file and Metadata generation is managed via the PCS Task Wrapper framework. The innovation is responsible for marshalling output Products and Metadata back to a PCS File Management component for use in downstream data processing and pedigree. In support of this, the PCS Task Wrapper leverages the PCS Crawler Framework to ingest (during pipeline processing) the output Product files and Metadata produced by the PGE. The architectural components of the PCS Task Wrapper framework include PGE Task Instance, PGE Config File Builder, Config File Property Adder, Science PGE Config File Writer, and PCS Met file Writer. This innovative framework is really the unifying bridge between the execution of a step in the overall processing pipeline, and the available PCS component services as well as the information that they collectively manage.

Mattmann, Chris A.↗

NASA NTRS2012

Debris Disk Structure and Morphology as Revealed by Aggressive STIS Multi-Roll Coronagraphy: A New Look at Some Old Friends

We present new imaging results from a well-selected sample of II circumstellar debris disks, all with HST pedigree, using STIS visible-light 6-roll PSF-template subtracted coronagraphy (PSFTSC). These new observations, pushing HST to its highest levels of coronagraphic performance, simultaneously probe both the interior regions of these debris systems, with inner working distances < app 8 AU for half the stars in this sample (corresponding to the giant planet and Kuiper belt regions within our own solar system), and the exterior regions far beyond. These new images enable direct inter-comparison of the architectures of these exoplanetary debris systems in the context of our own Solar System: These observations also permit us, for the first time, to characterize material in these regions at high spatial resolution and identify disk sub-structures that are signposts of planet formation and evolution; in particular, asymmetries and non-uniform debris structures that signal the presence of co-orbiting perturbing planets, and dynamical interactions (e.g., resulting in posited small grain stripping and disk "pollution") with the ISM. We focus here on recently acquired and reduced images of he circumstellar debris systems about: AU Mic (edge-on, and @ 10 pc the closest star in our sample), HD 61005, HD 32297 and HD 15115 (all with morphologies strongly suggestive of ISM wind interactions), HD 181327 & HDI07146 (close to face-on with respectively narrow and broad debris rings), and MP Mus (a "mature" proto-planetary disk hosted by a cTTS). All of our objects were previously observed in the near-IR with inferior spatial resolution and imaging efficacy, but with NICMOS r = 0.3" inner working angle (IWA) comparable to STIS multi-roll coronagraphy. The combination of new optical and existing near-IR imaging can strongly constrain the dust properties, thus enabling an assessment of grain processing and planetesimal populations. These results will directly inform upon the posited planet formation mechanisms that occur after the approximately 10 My epoch of gas depletion, a time in our solar system when giant planets were migrating and terrestrial planets were forming, and directly test theoretical models of these processes. These observations lmiquely probe both into the interior regions of these systems and are sensitive to and spatially resolve low surface-brightness (SB) material at large stellocentric distances with spatial resolution comparable to ACS and with augmenting NICMOS near-IR disk photometry in hand.

Grady, Carol A↗

NASA NTRS2014

Robust Informatics Infrastructure Required For ICME: Combining Virtual and Experimental Data

With the increased emphasis on reducing the cost and time to market of new materials, the need for robust automated materials information management system(s) enabling sophisticated data mining tools is increasing, as evidenced by the emphasis on Integrated Computational Materials Engineering (ICME) and the recent establishment of the Materials Genome Initiative (MGI). This need is also fueled by the demands for higher efficiency in material testing; consistency, quality and traceability of data; product design; engineering analysis; as well as control of access to proprietary or sensitive information. Further, the use of increasingly sophisticated nonlinear, anisotropic and or multi-scale models requires both the processing of large volumes of test data and complex materials data necessary to establish processing-microstructure-property-performance relationships. Fortunately, material information management systems have kept pace with the growing user demands and evolved to enable: (i) the capture of both point wise data and full spectra of raw data curves, (ii) data management functions such as access, version, and quality controls;(iii) a wide range of data import, export and analysis capabilities; (iv) data pedigree traceability mechanisms; (v) data searching, reporting and viewing tools; and (vi) access to the information via a wide range of interfaces. This paper discusses key principles for the development of a robust materials information management system to enable the connections at various length scales to be made between experimental data and corresponding multiscale modeling toolsets to enable ICME. In particular, NASA Glenn's efforts towards establishing such a database for capturing constitutive modeling behavior for both monolithic and composites materials

Mutli-scale models↗

NASA NTRS2014

Probing for Exoplanets Hiding in Dusty Debris Disks: Disk Imaging, Characterization, and Exploration with HST-STIS Multi-roll Coronagraphy

Spatially resolved scattered-light images of circumstellar debris in exoplanetary systems constrain the physical properties and orbits of the dust particles in these systems. They also inform on co-orbiting (but unseen) planets, the systemic architectures, and forces perturbing the starlight-scattering circumstellar material. Using HST/STIS broadband optical coronagraphy, we have completed the observational phase of a program to study the spatial distribution of dust in a sample of ten circumstellar debris systems, and one "mature" protoplanetrary disk all with HST pedigree, using PSF-subtracted multi-roll coronagraphy. These observations probe stellocentric distances greater than or equal to 5 AU for the nearest systems, and simultaneously resolve disk substructures well beyond corresponding to the giant planet and Kuiper belt regions within our own Solar System. They also disclose diffuse very low-surface brightness dust at larger stellocentric distances. Herein we present new results inclusive of fainter disks such as HD92945 (F (sub disk) /F (sub star) = 5x10 (sup -5) confirming, and better revealing, the existence of a narrow inner debris ring within a larger diffuse dust disk. Other disks with ring-like sub-structures and significant asymmetries and complex morphologies include: HD181327 for which we posit a spray of ejecta from a recent massive collision in an exo-Kuiper belt; HD61005 suggested to be interacting with the local ISM; HD15115 and HD32297, discussed also in the context of putative environmental interactions. These disks, and HD15745, suggest that debris system evolution cannot be treated in isolation. For AU Mic's edge-on disk we find out-of-plane surface brightness asymmetries at greater than or equal to 5 AU that may implicate the existence of one or more planetary perturbers. Time resolved images of the MP Mus proto-planetary disk provide spatially resolved temporal variability in the disk illumination. These and other new images from our HST/STIS GO/12228 program enable direct inter-comparison of the architectures of these exoplanetary debris systems in the context of our own Solar System.

stellocentric distances↗

NASA NTRS2016

Information Management Workflow and Tools Enabling Multiscale Modeling Within ICME Paradigm

With the increased emphasis on reducing the cost and time to market of new materials, the need for analytical tools that enable the virtual design and optimization of materials throughout their processing - internal structure - property - performance envelope, along with the capturing and storing of the associated material and model information across its lifecycle, has become critical. This need is also fueled by the demands for higher efficiency in material testing; consistency, quality and traceability of data; product design; engineering analysis; as well as control of access to proprietary or sensitive information. Fortunately, material information management systems and physics-based multiscale modeling methods have kept pace with the growing user demands. Herein, recent efforts to establish workflow for and demonstrate a unique set of web application tools for linking NASA GRC's Integrated Computational Materials Engineering (ICME) Granta MI database schema and NASA GRC's Integrated multiscale Micromechanics Analysis Code (ImMAC) software toolset are presented. The goal is to enable seamless coupling between both test data and simulation data, which is captured and tracked automatically within Granta MI®, with full model pedigree information. These tools, and this type of linkage, are foundational to realizing the full potential of ICME, in which materials processing, microstructure, properties, and performance are coupled to enable application-driven design and optimization of materials and structures.

Materials Engineering↗

NASA NTRS2017

The Integrated Medical Model: Outcomes from Independent Review

In 2016, the Integrated Medical Model (IMM) v4.0 underwent an extensive external review in preparation for transition to an operational status. In order to insure impartiality of the review process, the Exploration Medical Capabilities Element of NASA's Human Research Program convened the review through the Systems Review Office at NASA Goddard Space Flight Center (GSFC). The review board convened by GSFC consisted of persons from both NASA and academia with expertise in the fields of statistics, epidemiology, modeling, software development, aerospace medicine, and project management (see Figure 1). The board reviewed software and code standards, as well as evidence pedigree associated with both the input and outcomes information. The board also assesses the models verification, validation, sensitivity to parameters and ability to answer operational questions. This talk will discuss the processes for designing the review, how the review progressed and the findings from the board, as well as summarize the IMM project responses to those findings. Overall, the board found that the IMM is scientifically sound, represents a necessary, comprehensive approach to identifying medical and environmental risks facing astronauts in long duration missions and is an excellent tool for communication between engineers and physicians. The board also found IMM and its customer(s) should convene an additional review of the IMM data sources and to develop a sustainable approach to augment, peer review, and maintain the information utilized in the IMM. The board found this is critically important because medical knowledge continues to evolve. Delivery of IMM v4.0 to the Crew Health and Safety (CHS) Program will occur in the 2017. Once delivered for operational decision support, IMM v4.0 will provide CHS with additional quantitative capability in to assess astronaut medical risks and required medical capabilities to help drive down overall mission risks.

medical equipment↗

NASA NTRS2011

End-of-Life Optical Property Predictions of White Conductive Thermal Control Coatings through Analysis of On-Orbit and Ground Based Testing Data

New system requirements pertaining to thermal optical properties and coating electrical properties are commonly specified on non-low earth orbit missions. An increasing number of projects are specifying coatings with a surface resistivity of less than lE-9 ohm/square to mitigate electrostatic charge buildup events over a range of operational temperatures. There are a limited number of coatings that. meet these electrical property requirements while having flight derived optical properties in representative environments. Goddard Space Flight Center Code 546, Contamination and Thermal Coatings Group has recently explored the variety of electrically conductive white coatings available through domestic vendors to evaluate properties to meet project requirements in a geostationary orbit. The lack of significant flight data in representative environments required the careful selection of samples in ground based tests to establish end of life thermal properties. Attention must be given to the origin and pedigree of samples used on past on-orbit experiments to insure that the present formulations for the materials are similar and will react in similar manner.

Hasegawa, Mark↗

NASA NTRS2018

Wide-Field Infrared Survey Telescope (WFIRST) - Optical Telescope Assembly (OTA) Status

The WFIRST Mission is the next large astrophysical observatory for NASA after the James Webb Space Telescope and is the top priority mission from the 2010 National Academy of Sciences' decadal survey. The WFIRST OTA includes the inherited primary and secondary mirrors with precision metering structures that are to be integrated to new mirror assemblies to provide optical feeds to the two WFIRST science instruments. We present here: (1) the results for the review of the inherited hardware for WFIRST through a thorough technical pedigree process, (2) the status of the effort to establish the capability of the telescope to perform at a cooler operational temperature of 265K, and (3) the status of the work in requirement development for OTA to incorporate the inherited hardware, and (4) the path forward.

telescopes↗

NASA NTRS2018

Integration of Information Management System, Workflow and Computational Tools Enabling Multiscale Modeling Within an ICME Paradigm

With the increased emphasis on reducing the cost and time to market of new materials, the need for analytical tools that enable the virtual design and optimization of materials throughout their processing - internal structure - property - performance envelope, along with the capturing and storing of the associated material and model information across its lifecycle, has become critical. This need is also fueled by the demands for higher efficiency in material testing; consistency, quality and traceability of data; product design; engineering analysis; as well as control of access to proprietary or sensitive information. Fortunately, material information management systems and physics-based multiscale modeling methods have kept pace with the growing user demands. Herein, recent efforts to develop a set of Python functions that exchange information between NASA GRC's Integrated multiscale Micromechanics Analysis Code (ImMAC) software toolset and its Integrated Computational Materials Engineering (ICME), Granta MI® database schema is presented. The goal is to enable seamless coupling between both test data and simulation data, which is captured and tracked automatically within Granta MI®, with full model pedigree information. These tools, and this type of linkage, are foundational to realizing the full potential of ICME, in which materials processing, microstructure, properties, and performance are coupled to enable application-driven design and optimization of materials and structures.

multiscale modeling; Micromechanics; Computational↗

NASA NTRS2019

Gateway Modeling and Simulation Plan

This plan institutes direction across the Gateway Program and the Element Projects to ensure that Cross Program M&S are produced in a manner that (1) generate the artifacts required for NASA-STD-7009 compliance, (2) ensures interoperability of M&S exchanged and integrated across the program and, (3) drives integrated development efforts to provide cross-domain integrated simulation of the Gateway elements, space environment, and operational scenarios. This direction is flowed down via contractual enforcement to prime contractors and includes both the GMS requirements specified in this plan and the NASASTD- 7009 derived requirements necessary for compliance. Grounding principles for management of Gateway Models and Simulations (M&S) are derived from the Columbia Accident Investigation Board (CAIB) report and the Diaz team report, “A Renewed Commitment to Excellence.” As an outcome of these reports, and in response to Action 4 of the Diaz team report, the NASA Standard for Models and Simulations, NASA-STD-7009 was developed. The standard establishes M&S requirements for development and use activities to ensure proper capture and communication of M&S pedigree and credibility information to Gateway program decision makers. Through the course of the Gateway program life cycle M&S will be heavily relied upon to conduct analysis, test products, support operations activities, enable informed decision making and ultimately to certify the Gateway with an acceptable level of risk to crew and mission. To reduce risk associated with M&S influenced decisions, this plan applies the NASA-STD-7009 requirements to produce the artifacts that support credibility assessments and ensure the information is communicated to program management.

NASA-STD-7009↗

NASA NTRS2017

Forward Contamination of Ocean Worlds: A Stakeholder Conversation

A fundamental requirement for space missions designed to touch “potential habitats” is the single number 10−4, the allowable probability of a single Earth organism contaminating the potential habitat. Many aspects of a mission that affect its complexity and cost – hardware design and manufacture, assembly and test, and mission operations – are driven by this value, so it is important, on the threshold of an era of exploring ocean worlds, to have confidence in it. Yet despite its long pedigree and occasional reviews, we find that the current requirement lacks programmatically defensible justification. At issue are three weaknesses: 1) microbial biology, in particular the science of extremophiles, is a rapidly changing field; 2) forward contamination is both a scientific and an ethical issue, yet no ethics-based conversation is apparent within policy-setting circles; 3) because of these two factors, policy-setting cannot be static. We review the history of the requirement; how the evolving understanding of biology could drive it up or down; how the forward-contamination hazard relates to risk-management practice and to the ethics profession; and how a contemporary stakeholder conversation could adapt lessons already learned by other fields.

Waltemathe, Michael↗

NASA NTRS2022

Low-Earth Orbit Trajectory Optimization in the Presence of Atmospheric Uncertainty

The previous 20 to 25 years have seen a tremendous increase in space exploration, and with that an increase in the level of logistics planning needed to ensure mission success. For spacecraft that are designed to be periodically re-supplied, a key logistics consumable is propellant, as it constitutes the greatest up-mass on re-supply vehicles. A trajectory design strategy is therefore desired that minimizes propellant usage in order to ease the demand for propellant re-supply missions. This thesis develops such a strategy in three stages, and uses the International Space Station (ISS) as its testbed, as no other LEO spacecraft is more challenging from a space logistics standpoint. First, the ISS trajectory planning problem is formulated as a constrained burn optimization problem assuming a deterministic atmosphere. The cost function is total ∆v, with constraints imposed on longitude of ascending viii node (LAN) and semi-major axis (SMA) altitude. Analytic derivatives are constructed for both the cost and constraints, which are necessary given the 6-week to 2-year time frames being considered. A gradient-based optimizer is then utilized to find locally-optimal solutions to real-world ISS trajectory planning problems. Second, atmospheric uncertainty is addressed by constructing a probabilistic model of space weather data using Gaussian Processes (GPs). Bayesian inference is performed using the GP model to generate mean and covariance estimates for space weather predictions, whose pedigree is assessed against test data. The predictions are then mapped into atmospheric density via the analytic Jacchia-Roberts density model, and the effect of space weather uncertainty on orbital lifetime is examined. Third, an ISS burn execution uncertainty model is developed. This model, along with the space weather uncertainty model, are deployed in a linear covariance analysis to ascertain their combined effect on LAN and SMA altitude dispersions. The deterministic constraints from the original problem are re-formulated as stochastic constraints, where now the constraint uncertainty interval is required to fall within specified bounds. An updated optimization framework is constructed using the original ∆v cost function along with the stochastic constraints to solve the trajectory optimization problem under atmospheric uncertainty. Finally, the complete architecture is summarized for deployment in an operational setting.

Trajectory Optimization↗

NASA NTRS2023

NASA GRC ICME Schema for Materials Data Management: An Executive Summary

Integrated Computational Materials Engineering (ICME) has received a growing emphasis in attention due its potential impact on rapid material design, reduction in cost and time to market for new applications, and the promise of ‘fit-for-purpose’ materials coupled with recent advances in high performance computing and material characterization tools. However, for an organization to implement ICME practices for material discovery and design, a series of both technical and cultural challenges must be overcome to foster an environment that enables efficient, traceable, and predictive multiscale simulations of material behavior to enable virtual design of materials. In 2016, NASA sponsored a 2040 Vision study to define the potential 25-year future state required for integrated multiscale modeling of materials and systems to improve both the associated time and cost for aerospace and aeronautical innovation. The study envisions a cyber-physical-social ecosystem of experimentally validated computational models, tools, and techniques, along with the associated digital tapestry, that can enable rapid, optimized, ‘fit-for-purpose’ design of materials, components, and systems. A key requirement for such an ecosystem is the development of a robust information management system for materials across their full lifecycle, including material pedigree, experimental (real) and virtual (simulation) data, developed material models, and the implementation of models in engineering applications, such that process-structure-property-performance relationships can be established, thereby enabling the virtual design and optimization of materials. Such an information management system must be able to effectively capture: i) material information at each length scale; ii) test data and analysis; iii) associated material models; and iv) material and model deployment in engineering applications. These systems must also provide traceability between experimental and virtual representations of the material to ensure, when appropriate, the material digital twin is maintained. Additionally, this robust material information management system must be able to seamlessly connect with both commercial and an organization’s in-house software tools, be they analysis tools, other material databases, product lifecycle management (PLM) or simulation data management (SDM) tools, etc., such that automation of the design and analysis of a material across multiple length scales is possible. In this paper, an executive summary of the NASA GRC ICME Schema for materials information management is presented. The database best practices and schema design philosophy specifically for ICME materials data management and an overview description of each element in the schema is given, along with its associated role in an ICME workflow. Additionally, auxiliary tools that interact with the database and provide judicious automation with regards to importing, exporting, and analyzing materials data are presented. Such tools are critical to an ICME ecosystem, not only for their role in enabling optimization, but also in relieving users of tedious manual tasks, thus helping to promote adoption and combat the cultural challenges organizations face in enabling ICME.

Materials↗

NASA NTRSDate not supplied

Establishing and Maintaining the Digital Thread of Additively Manufactured Materials and Applications

Additive Manufacturing (AM) and Integrated Computational Materials Engineering (ICME) are complementary enabling technologies for design and manufacturing of “fit-for-purpose” materials. Both technologies will impact rapid material design, reduction in cost- and time-to-market for new applications, and discovery and implementation of new materials. An ICME approach to design, however, requires experimentally validated material models at multiple length and time scales, an integrated framework that can connect analysis tools with one another to ensure the digital thread of an application is maintained, and the manufacturing (e.g., AM) capability to leverage processing-structure-property-performance (PSPP) relationships to achieve spatially varying material properties where desired. AM enables the implementation of the design of an optimized, spatially varying microstructure through careful selection of the processing parameters used during an additively manufactured build. In order to establish these PSPP relations, a large amount of data is necessary, and that data must be properly captured, analyzed and maintained in an information management system that can establish the required traceability between various aspects of the design process to ensure an application’s digital thread is maintained (from design to end of life). Such an information management system must be able to capture feedstock material pedigree, resulting microstructure from various build parameters, subsequent mechanical properties derived from testing, developed material models, and enable spatial variations in material assignment in an engineering application. Furthermore, the information management system should be easily integrated with traditionally engineered materials in a single, centralized platform to enable an ICME optimization tool to explore both types of manufacturing processes. At NASA GRC, a robust, 21st century materials information management system has been previously developed with a focus towards enabling ICME. In this work, GRC’s ICME schema is extended to accommodate additively manufactured materials, enabling storage of both traditionally and additively manufactured materials in the same construct. The methodology for properly capturing additively manufactured materials across the entire material lifecycle is presented, following the previously established database best practices, as a potential framework for establishing PSPP relationships for additively manufactured materials and applying them to engineering applications.

Data management↗

NASA NTRSDate not supplied

Py MILab: Capturing, Analyzing and Storing Test Data

Integrated Computational Materials Engineering (ICME) has recently received widespread attention due to its promises in reducing dependence on physical testing for engineering design by relying on simulation, reducing both time and cost to market for various applications. ICME however requires validated multiscale material models, which is heavily dependent on available test data with full material and test pedigree, including material processing, test and measurement equipment, raw data collection, and analysis methodology and results. Populating searchable information management systems with such rich data sets is often burdensome for data producers, resulting in a lack of findable data for modelers to validate and verify their models. To overcome these cultural barriers to ICME, NASA has developed of various database-integration toolsets that perform both data management activities within the organization’s best practices with additional functionality that relieves the effort of the data producer and promotes adoption of information management system. One such tool currently under development is Py MILab, an automatic framework for automatic capturing, analysis, maintenance, and storage of material test data. Py MILab uses a modular approach for capturing raw data, analyzing the data, and storing the data in a database, interfaced by neutral file structures, to promote plug-and-play capabilities for various analysis types. TMAnalysis is a Python-based tool that performs automatic data reduction and analysis of uniaxial thermomechanical test data. The TMAnalysis toolset can be implemented within the Analysis module of Py MILab, and thus requires a populated neutral file form the Raw Data Module of Py MILab and outputs a Analysis neutral file compatible with the Database Module of Py MILab. TMAnalysis is able to perform automatic segmentation of multistage tests and perform data analysis and reduction, including determination of point-wise properties in tension, compression, and shear, analysis of stress relaxation tests, creep analysis and zone identification, and combination of these stage types for tests with complex loading histories. The TMAnalysis code is accompanied with a graphical user interface (GUI) that allows users to easily analyze test data in bulk, verify the automatic, consistent analysis performed by the backend code, and edit stage segmentation if necessary before producing the output neutral files, ensuring data is properly analyzed and maintained with full traceability.

Data management↗

NASA NTRSDate not supplied

Materials Informatics at NASA GRC: Machine Learning Surrogate Modeling, Data Management, and Integrated Toolsets for Establishing/Maintaining the Digital Thread

Machine Learning↗

NASA NTRS2003

Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

Non-NASA Center↗

NASA NTRS2002

Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency

Norepinephrine (NE), a key neurotransmitter of the central and peripheral nervous systems, is synthesized by dopamine beta-hydroxylase (DBH) that catalyzes oxidation of dopamine (DA) to NE. NE deficiency is a congenital disorder of unknown etiology, in which affected patients suffer profound autonomic failure. Biochemical features of the syndrome include undetectable tissue and circulating levels of NE and epinephrine, elevated levels of DA, and undetectable levels of DBH. Here, we report identification of seven novel variants including four potentially pathogenic mutations in the human DBH gene (OMIM 223360) from analysis of two unrelated patients and their families. Both patients are compound heterozygotes for variants affecting expression of DBH protein. Each carries one copy of a T-->C transversion in the splice donor site of DBH intron 1, creating a premature stop codon. In patient 1, there is a missense mutation in DBH exon 2. Patient 2 carries missense mutations in exons 1 and 6 residing in cis. We propose that NE deficiency is an autosomal recessive disorder resulting from heterogeneous molecular lesions at DBH. Copyright 2002 Wiley-Liss, Inc.

Case Reports↗