Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan.

The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.

Transvestism Recognized in Ehlers-Danlos Syndrome: Report of Two Cases.

Ehlers-Danlos syndrome (EDS) comprises a series of rare hereditary connective tissue diseases characterized by musculoskeletal, skin, and cardiovascular involvements. EDS may be associated with physical as well as psychological pain that can lead to psychiatric problems. EDS imposes substantial psychological burden on patients, and recent large-scale studies have suggested that patients with EDS have a higher risk of mood disorders than the general population. To the best of our knowledge, we describe, for the first time, the cases of two Japanese patients with EDS complicated with mood disorders who secondarily developed transvestism that was judged strongly related to early stressful situations through childhood and adolescence. The first case was of a man in his mid-30s and the second of a woman in her late 20s. We report on detailed psychosocial data to further discuss the medical management and genetic counseling of such infrequent but challenging conditions. Physicians are advised to be aware of various potential psychological and psychiatric issues that may accompany EDS.

Antimicrobial effect of an ultrasonic levitation washer disinfector with silver electrolysis and ozone oxidation on methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has rapidly emerged as a cause of severe and intractable skin infection. At present, there are no effective topical treatments, and infection or colonization by MRSA of the skin raises serious medical problems. We developed an ultrasonic levitation washer that generates silver ions (Ag(+)) and ozone (O3) to clean and sterilize medical devices. We report the effect of ultrasonic levitation (levitation) with Ag(+) and O3 on MRSA in vitro and in vivo. Antimicrobial effect against six MRSA strains of all agr types was examined under three in vitro conditions; cells floating in a water tank, cells infiltrating-, and cells forming a biofilm on an atelocollagen membrane. In the in vivo studies, we assayed the number of MRSA organisms that survived treatment on murine skin ulcers and evaluated the ulcer size. Levitation with Ag(+) dramatically decreased the survival of MRSA floating in a water tank. Levitation with Ag(+) and O3 significantly decreased the viability of MRSA that had infiltrated or formed a biofilm on atelocollagen membranes regardless of the level of biofilm production. In vivo studies showed that the number of MRSA on murine skin ulcers was significantly decreased when 15-min treatment was performed for 7 consecutive days and that the ulcer size was significantly decreased after the seventh treatment course. Levitation with Ag(+) and O3 may be a valuable tool for treating MRSA infestation of the skin and for accelerating wound healing.

Follow-up nationwide survey on predictive genetic testing for late-onset hereditary neurological diseases in Japan.

A follow-up nationwide survey on predictive genetic testing for late-onset neurological diseases in Japan was conducted. A questionnaire was sent to 89 institutional members of the Japan's National Liaison Council for Clinical Sections of Medical Genetics, and was returned by 60 (67.4%). A total of 301 clients with an interest in predictive testing were accumulated from April 2006 to March 2011. The greatest interest was shown for spinocerebellar degeneration (SCD, n=110), followed by myotonic dystrophy type 1 (DM1, n=69), Huntington's disease (HD, n=52) and familial amyloid polyneuropathy (FAP, n=35). The ratios of clients who actually underwent predictive testing were: SCD, 21.8%; DM1, 39.1%; HD, 26.9%; and FAP, 74.3%, indicating that predictive testing was conducted very cautiously for untreatable neurological diseases in Japan. Clinical geneticists were predominantly involved in genetic counseling, whereas the participation of non-medical doctor (non-MD) staff, including nurses, clinical psychologists and genetic counselors, was not common. Lack of non-MD counseling staff was one of the most serious issues in conducting predictive testing, which has not been improved since the previous survey performed in 2006. Institutional arrangements, such as revision of medical insurance system regarding genetic testing and counseling, might be necessary to resolve this issue.

[Current status of the predictive genetic testing for hereditary neurological diseases in Shinshu University Hospital].

The current status of predictive genetic testing for late-onset hereditary neurological diseases in Japan is largely unknown. In this study, we analyzed data from 73 clients who visited the Division of Clinical and Molecular Genetics, Shinshu University Hospital, for the purpose of predictive genetic testing. The clients consisted of individuals with family histories of familial amyloid polyneuropathy (FAP; n=30), Huntington's disease (HD; n=16), spinocerebellar degeneration (SCD; n=14), myotonic dystrophy type 1 (DM1; n=9), familial amyotrophic lateral sclerosis type 1 (ALS1; n=3), and Alzheimer's disease (AD; n=1). Forty-nine of the 73 (67.1%) clients were in their twenties or thirties. Twenty-seven of the 73 (37.0%) clients visited a medical institution within 3 months after becoming aware of predictive genetic testing. The most common reason for requesting predictive genetic testing was a need for certainty or to reduce uncertainty and anxiety. The decision-making about marriage and having a child was also a main reason in clients in the twenties and thirties. The numbers of clients who actually underwent predictive genetic testing was 22 of 30 (73.3%) in FAP, 3 of 16 (18.8%) in HD, 6 of 10 (60.0%) in SCD, 7 of 9 (77.8%) in DM1, and 0 of 3 (0%) in ALS1 (responsible gene of the disease was unknown in 4 SCD patients and an AD patient). The percentage of test usage was lower in untreatable diseases such as HD and SCD than that in FAP, suggesting that many clients changed their way of thinking on the significance of testing through multiple genetic counseling sessions. In addition, it was obvious that existence of disease-modifying therapy promoted usage of predictive genetic testing in FAP. Improvement of genetic counseling system to manage predictive genetic testing is necessary, as consultation concerning predictive genetic testing is the main motivation to visit genetic counseling clinic in many at-risk clients.

[Analysis of 14 individuals who requested predictive genetic testing for hereditary neuromuscular diseases].

Predictive genetic testing for hereditary neuromuscular diseases is a delicate issue for individuals at risk and their families, as well as for medical staff because these diseases are often late-onset and intractable. Therefore careful pre- and post-test genetic counseling and psychosocial support should be provided along with such genetic testing. The Division of Clinical and Molecular Genetics was established at our hospital in May 1996 to provide skilled professional genetic counseling. Since its establishment, 14 individuals have visited our clinic to request predictive genetic testing for hereditary neuromuscular diseases (4 for myotonic dystrophy, 6 for spinocerebellar ataxia, 3 for Huntington's disease, and 1 for Alzheimer's disease). The main reasons for considering testing were to remove uncertainty about the genetic status and to plan for the future. Nine of 14 individuals requested testing for making decisions about a forthcoming marriage or pregnancy (family planning). Other reasons raised by the individuals included career or financial planning, planning for their own health care, and knowing the risk for their children. At the first genetic counseling session, all of the individuals expressed hopes of not being a gene carrier and of escaping from fear of disease, and seemed not to be mentally well prepared for an increased-risk result. To date, 7 of the 14 individuals have received genetic testing and only one, who underwent predictive genetic testing for spinocerebellar ataxia, was given an increased-risk result. The seven individuals including the one with an increased-risk result, have coped well with their new knowledge about their genetic status after the testing results were disclosed. None of them has expressed regret. In pre-test genetic counseling sessions, we consider it quite important not only to determine the psychological status of the individual, but also to make the individual try to anticipate the changes in his/her life upon receiving an increased-risk or a decreased-risk result. Sufficient time should be taken to build a good relationship between the individual and his/her family and the medical staff during pre-test counseling sessions. This will help the individuals feel satisfied with their own decisions for the future, whether they receive genetic testing or not.

[Patients' evaluation of information provided by medical doctors on the invasive ventilator for amyotrophic lateral sclerosis. An analysis of a survey of patients and their families in Japan].

OBJECTIVE: The study aim was to evaluate by ALS patients' satisfaction regarding information about invasive ventilators provided by medical doctors. METHODS: Semi-structural interviews were conduced for 12 cases (11 patients and 9 family members provided information) at three areas in Japan. RESULTS: 1) Most patients were unsatisfied with the information by doctors; 2) some cases felt strong distrust of doctors' attitudes; 3) more than half of the cases complained of insufficient information. CONCLUSION: This study suggests that in the informed consent for ALS patients, doctors' negative attitudes to life prolongation adversely impact on ALS patients. Roles of service providers, patients and family members should be reconsidered for cases of ALS and other incurable diseases.