The different nutritional properties of several Desulfovibrio desulfuricans strains suggest that either the strains are misclassified or there is a high degree of phenotypic diversity within the genus Desulfovibrio. The obligately anaerobic, dissimilatory, sulfate-reducing bacteria utilize sulfate as their terminal electron acceptor and derive their energy for growth from the oxidation of organic compounds and hydrogen gas (27). Among the genera of sulfate-reducing bacteria, perhaps the most thoroughly studied species are classified in the genus Desulfovibrio. The Desulfovibrio species which have been characterized are nutritionally similar; they are readily enriched with lactate or hydrogen and utilize only a few other substrates (38). Diagnostically, Desulfovibrio species test positive (with some exceptions) for the sulfite reductase desulfoviridin and contain the unique tetraheme cytochrome C3 (27). These observations have contributed to the notion that although the sulfate-reducing bacteria are ecologically very significant, they comprise a small and nutritionally limited group. However, recent isolations and descriptions of new genera have dispelled this view (38). At present, more than 10 genera of sulfate-reducing eubacteria (one of which is affiliated with gram-positive bacteria) and an extremely thermophilic sulfate-reducing archaebacterium have been described (36, 39).While the nutritional versatility and phylogenetic diversity of the sulfate-reducing bacteria have been established, questions of relatedness among species of the genus Desulfovibrio remain unanswered. Postgate has stated that the "taxonomic picture" of the genus is "imperfect" (27

Percentage of respondents who reported testing for each gene specified in the survey. The total number of respondents who reported testing for specific ALS genes was 41 (of 43 who responded to the survey). jamaneurology.com (Reprinted) JAMA Neurology

Background: A genetic basis is found in ~70% of familial and ~15% of sporadic ALS, in research cohorts. Clinical trials of gene-targeted therapies are underway, heralding a new era of personalized medicine in ALS treatment. However, ALS management guidelines do not include recommendations for the offer of genetic testing. Many persons with ALS who desire genetic testing are not currently offered it, and the yield of genetic testing in clinic-based ALS populations is unknown. The ALS GAP program, sponsored by the Northeast ALS (NEALS) Consortium, provides free genetic testing for patients with ALS who have a family history of ALS or dementia. We report genetic testing outcomes in the first 142 patients tested in the program. Objectives: 1) To create a pilot ALS genetic testing program for NEALS clinics, 2) To study the rate of ALS gene identification in a US clinic-based population Methods: Persons with ALS and a family history of ALS (fALS) or dementia (dALS) who receive care at a US NEALS clinic are eligible for testing. Patients classified as fALS (having a positive family history of ALS in a 1 st , 2 nd , or 3 rd degree relative) are eligible for C9orf72 testing, with the option to reflex to a 5 gene (SOD1, FUS, TARDBP, TBK1, VCP) panel. Patients classified as dALS (having a positive family history of dementia of any type in a 1 st or 2 nd degree relative) are eligible for C9orf72 testing only. Results: Currently, 29.5% (34/115) of US NEALS clinics have participated in the program. Of 142 patients who have completed testing to date, 78 (54.9%) were classified as fALS and 64 (45.1%) as dALS. Among fALS cases, 42/78 (53.9%) tested positive, including 32/78 (41%) with a C9orf72 repeat expansion, and 10/78 (12.8%) with other pathogenic or likely pathogenic variants in SOD, FUS, TARDP or VCP. Variants of uncertain significance (VUS) in FUS were identified in 2/78 (2.6%). Among dALS cases, 12/60 (20%) tested positive for C9orf72. Discussion and conclusions: Participation in ALS-GAP indicates significant clinician and patient interest in ALS genetic testing. This program addresses several current barriers to testing access, including cost, identifying appropriate candidates for testing, and appropriate test selection. Although 38% of patients who participated in the program have thus far received a genetic diagnosis, our testing outcome data suggests that the gene identification rate in fALS cases may be lower in clinic-based patients than in research cohorts, particularly for genes other than C9orf72. This program may serve as a model for the practice of ALS genetic testing in the clinic setting. Consistent, equitable testing policies, as well as an accurate understanding of the genetic profile of clinic-based ALS populations, are needed as gene-targeted therapies reach patient care. GEN-02 A clinical tool to determine the probability of a person with ALS having a positive gene test, given their age of onset