Targeted exome sequencing of suspected mitochondrial disorders.

OBJECTIVE: To evaluate the utility of targeted exome sequencing for the molecular diagnosis of mitochondrial disorders, which exhibit marked phenotypic and genetic heterogeneity. METHODS: We considered a diverse set of 102 patients with suspected mitochondrial disorders based on clinical, biochemical, and/or molecular findings, and whose disease ranged from mild to severe, with varying age at onset. We sequenced the mitochondrial genome (mtDNA) and the exons of 1,598 nuclear-encoded genes implicated in mitochondrial biology, mitochondrial disease, or monogenic disorders with phenotypic overlap. We prioritized variants likely to underlie disease and established molecular diagnoses in accordance with current clinical genetic guidelines. RESULTS: Targeted exome sequencing yielded molecular diagnoses in established disease loci in 22% of cases, including 17 of 18 (94%) with prior molecular diagnoses and 5 of 84 (6%) without. The 5 new diagnoses implicated 2 genes associated with canonical mitochondrial disorders (NDUFV1, POLG2), and 3 genes known to underlie other neurologic disorders (DPYD, KARS, WFS1), underscoring the phenotypic and biochemical overlap with other inborn errors. We prioritized variants in an additional 26 patients, including recessive, X-linked, and mtDNA variants that were enriched 2-fold over background and await further support of pathogenicity. In one case, we modeled patient mutations in yeast to provide evidence that recessive mutations in ATP5A1 can underlie combined respiratory chain deficiency. CONCLUSION: The results demonstrate that targeted exome sequencing is an effective alternative to the sequential testing of mtDNA and individual nuclear genes as part of the investigation of mitochondrial disease. Our study underscores the ongoing challenge of variant interpretation in the clinical setting.

Research in clinical laboratory science: professionals' involvement.

OBJECTIVES: To describe current qualitative and quantitative aspects of research engagement and other scholarly activities conducted by clinical laboratory science (CLS) professionals across a range of employment settings. DESIGN: A link to a 3-part online survey was sent by electronic mail to 7,572 members of the American Society for Clinical Laboratory Science and 500 program directors. SETTING: email message, on-line survey PARTICIPANTS: all ASCLS members and all directors of accredited clinical laboratory educational programs MAIN OUTCOME MEASURES: Quantitative and qualitative measures of professionals' engagement in research and other scholarly activities RESULTS: 556 of 7572 (7.3%) persons completed the survey. Thirty-two percent of survey respondents reported spending between 1 to > 40 work hours per week conducting research with 68% of respondents not participating in research activities. Conducting research is an employment requirement for 18% of survey participants. Twenty-nine percent of respondents have published at least one research article, and 47% of respondents who conduct research have published studies in the journal Clinical Laboratory Science. More than 57% of respondents participate in non-research scholarly activities as part of their employment. CLS professionals who conduct research are more likely to do applied, clinical, or educational research than other types of research. Fifty-seven percent of respondents who conduct research lack external funding for their work. Ninety-three percent of total research dollars is obtained by respondents who hold the Ph.D. degree. The perception of the importance of conducting research varies by employment position. Barriers to participation in research include lack of inclusion of research in the job description, time constraints, inadequate research funding, limited opportunity, and lack of space and equipment. CONCLUSIONS: CLS professionals participate in research in limited numbers, and are more likely to engage in non-research types of scholarly activities. Numerous barriers are identified which impose limits to conducting research. Over half of CLS's research efforts lack external funding. Although there was broad representation among participants across educational levels, employment settings, and job positions, the number of survey respondents was limited. Possible directions for future research include conducting this survey using members of additional professional organizations.

Research in clinical laboratory science: professionals' educational preparation.

OBJECTIVE: To describe the educational preparation of CLS professionals for conducting research. DESIGN: A link to 3-part online survey was sent by electronic mail to 7,572 members of the American Society for Clinical Laboratory Science and 500 program directors research project. Barriers to participation in research by undergraduates include time limitations within the curriculum, insufficient faculty time, and lack of funds, space, and equipment. Increased emphasis on developing research skills is found in educational programs at the master's degree level. CONCLUSIONS: The formal educational background of many CLS professionals may leave them unprepared or underprepared for conducting research. Although there was broad representation among participants across educational levels, employment settings, and job positions, the number of survey respondents was limited. Possible directions for future research include conducting this survey using members of additional professional organizations.

ASCLS members perceptions regarding research.

One of the benchmarks of a profession is performing, publishing, and presenting research. However, in the Clinical Laboratory Science (CLS) profession, few manuscripts are submitted to the American Society for Clinical Laboratory Science (ASCLS) journal, Clinical Laboratory Science, on a regular basis. The problem is that perceptions regarding research, and the role of laboratory professional as researchers, held by ASCLS members may be contributing to the low number of manuscript submissions. To assess these perceptions, an anonymous Likert-scale survey was developed and delivered online using Survey Monkey. Members of ASCLS, with email addresses, were chosen to participate in this survey because they may be most likely to contribute manuscripts for a journal by their own society. About 10% of the 7,000 members who were invited by email chose to participate in this study. Most participants agreed that 1) there is important information to be gathered from research on clinical laboratory specimen results (99.6%), 2) research contributes valuable information to the body of CLS knowledge (99.2%), and 3) conducting research is one of the benchmarks of a profession (92.4%). The majority of participants felt that there are inadequate resources (68.8%) and not enough time (83%) available to conduct research in the clinical laboratory setting. Most participants recognize that many laboratory activities constitute research (86.2%), but only a few are willing to publish research findings on their own (29.2%). Those who are the most likely to publish research findings include men, university faculty, and members who are over 60 years old. University faculty are the most likely to assist others in the writing process. These results show an opportunity exists for ASCLS to foster collaborations between bench technologists and educators willing to assist with the publication process.