NINDS Repository Motor Neuron Disease/ALS Study

The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (the NINDS Repository), banks phenotypic data and biological samples, including from individuals with motor neuron disease, in order to facilitate gene discovery in neurological disorders. Those samples are used in a number of studies, and genotyping data from studies using this resource are encouraged to be shared via dbGaP. Many studies have already shared data in this fashion, which in turn, can be linked back to the biologicals banked at the NINDS Repository. Motor Neuron Disease is characterized by selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In Amyotrophic Lateral Sclerosis (ALS), there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes, the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy, the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation (Adams et al, Principles of Neurology, 6th ed, p 1089). The Motor Neuron Disease Collection of DNA and cell lines in the NINDS Repository is largely Amyotrophic Lateral Sclerosis cases (others include progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy, Kennedy's disease). Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). Although ALS is the most common MND, it is still a relatively rare disease with an incidence of around 1.6 per 100,000 in the United States. It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered (including SOD1). However, most forms of the disease are not obviously familial. It is suspected that the sporadic forms of neurodegenerative disorders are caused by multiple genetic variants that individually make relatively weak contributions to risk. There is also an associated Control collection (see dbGaP and Coriell). Studies in motor Neuron Disease may use cases from the NINDS repository, controls from the NINDS repository, as well as cases, and controls, from other sources. A subset of subjects from The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (the NINDS Repository): Motor Neuron/Amyotrophic Lateral Sclerosis (ALS) Study was utilized in the Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data study. Note: The publication Chio et al., 2009 states that "Raw sample-level genotype data from the initial GWAS study ... are available for download through the dbGAP portal (phs000006.v1.p1)". Instead, please follow this link: phs000101.v1.p1.]]>
MOTOR NEURON DISORDERS CLINICAL DATA ELEMENTSSAMPLE INFORMED CONSENT LANGUAGEParticipant Protection Policy FAQFor subject inclusion into the ALS collection, complete NINDS Repository Clinical Data Elements (CDEs) are required. These elements were developed to permit researchers using the specimens to apply to the El Escorial Criteria for the diagnosis of ALS at more than one level of stringency in a standardized fashion. Additionally, these were designed towards allowing broad pooling of multiple sample sets, since there are many international groups collecting samples for ALS gene discovery with which those from this effort could ultimately be pooled to achieve larger sample sizes and thus greater power to detect genes of risk. These CDEs also query exclusionary features, such as electrophysiological, CSF, imaging or other findings suggestive of confounding diagnoses. Data dictionaries have been designed by the collaboration (E. Kasarkis and K. Bednarz) and are publicly available to allow rapid referencing of all phenotypic terms at Coriell. For a given data element, the rules listed below were used to decide if the sample should be included in the collection. All required data must be present if a sample was included in the collection to ensure a standard data set for all samples. ElementRule Age or month/yrRequired: Must give one or other GenderRequired RaceRequired EthnicityRequired Age or month/yr of diagnosisRequired Age or month/yr of onset weaknessRequired Clinician sourceRequired Family historyRequired Medical historyMust check all that apply Primary clinical diagnosisRequired: Only one may be chosen Secondary clinical diagnosisRequired: Must check one or not applicable Site of onset weaknessRequired: Must check only one Current treatmentRequired: May be N/A or may be multiple Upper motor, lower motor, and emgRequired: Only one should be chosen GeneticsRequired: One or more must be checked. May be present, or absent. If present, then must specify mutation, give OMIM link. Atypical featuresOptional Please note that this information applies to cases with motor neuron disease (primarily ALS) from the NINDS Repository collection. However, many studies utilize one or more of the following in combination: cases from this NINDS Repository collection, cases from other sources, controls form the NINDS repository, controls from other sources. For more specifics regarding this, please see the specific sub-study or related study description. The NINDS Repository control collection and related studies are also described, and available via dbGaP at phs000004. ]]>
The NINDS repository was created in 2002 towards the goal of creating large sample size collections to allow the study of complex disease genetics. In 2004, ALS was added as one of the diseases banked. To facilitate complex gene discovery in ALS, the NINDS Repository (under a contract with Coriell Cell Repositories, # N01-NS-2-2349), in collaboration with The ALS Association (ALSA), The Muscular Dystrophy Association (MDA) and academic scientists from 62 centers across the United States, developed a program for evaluation of individuals affected with ALS, neurologically normal controls, and banking of their blood samples and clinical data. This unique public-private collaboration facilitated leverage of resources to develop this collection broadly across the United States. Many of the clinicians in this collaboration are members of the ALS Research Group (ALSRG) who collected samples under the supplement mechanism, NOT-NS-03-016. Investigators who had been collecting and banking samples as a part of the overall NINDS-funded effort in ALS gene discovery have also contributed to this effort, and continue to do so in an ongoing fashion. ]]>