Association Between White Matter Tract Integrity and Frontal-Executive Function in Non-Geriatric Adult Patients With Major Depressive Disorder.

OBJECTIVE: This study investigated the association between white matter tract integrity and frontal executive function in adult non-geriatric patients with major depressive disorder (MDD) and healthy controls (HCs) using diffusion tensor imaging (DTI). METHODS: In total, 57 patients with MDD and 115 HCs participated in this study. We calculated the integrity of the white matter tracts using the Tracts Constrained by Underlying Anatomy tool (TRACULA) from FreeSurfer. We performed cognitive function tests. Oneway analysis of covariance was used to investigate the DTI parameters as dependent variables; diagnosis of MDD as an independent variable; and age, sex, and education level as covariates. For correlation analysis between the DTI parameters and cognitive function tests, Pearson's partial correlation analyses were performed in the MDD and HC groups. RESULTS: The patients with MDD showed significantly decreased axial diffusivity (AD) in forceps major (FMajor), left corticospinal tract (CST), left superior longitudinal fasciculus-parietal bundle (SLFP), right anterior thalamic radiation (ATR), right CST, right inferior longitudinal fasciculus (ILF) and right superior longitudinal fasciculus-temporal bundle (SLFT) and mean diffusivity (MD) in the left CST, right CST, and right SLFT compared to HCs. We found that non-geriatric patients with MDD showed a significant negative correlation between the response time in the Stroop task and the AD value of the FMajor. CONCLUSION: Our findings suggest that impaired structural connectivity in the FMajor may be associated with cognitive dysfunction in non-geriatric patients with MDD.

Priming Mesenchymal Stem/Stromal Cells with a Combination of a Low Dose of IFN-γ and Bortezomib Results in Potent Suppression of Pathogenic Th17 Immunity Through the IDO1-AHR Axis.

Preconditioning of mesenchymal stem/stromal cells (MSCs) with the inflammatory cytokine IFN-γ enhances not only their immunosuppressive activity but also their expression of HLA and proinflammatory genes. We hypothesized that prevention of the upregulation of inflammatory cytokines and HLA molecules in IFN-γ-primed MSCs would render these cells more immunosuppressive and less immunogenic. In this study, we discovered the following findings supporting this hypothesis: (1) activated human T cells induced the expression of IDO1 in MSCs via IFN-γ secretion and those MSCs in turn inhibited T-cell proliferation in an AHR-dependent fashion; (2) there was no difference in the expression of IDO1 and HLA-DR in MSCs after priming with a low dose (25 IU/mL) versus a high dose (100 IU/mL) of IFN-γ; (3) the transient addition of bortezomib, a proteasome inhibitor, to culture MSCs after IFN-γ priming decreased the expression of HLA-DR, inflammatory cytokine genes and Vcam1 while increasing the expression of IDO1 and the production of L-kynurenine; finally, MSCs primed with a combination of a low dose of IFN-γ and bortezomib were more effective in inhibiting Th17-mediated idiopathic pneumonia syndrome (IPS) and chronic colitis than unprimed MSCs. Our results suggest that bortezomib significantly eliminates the unfavorable effects of IFN-γ priming of MSCs (increased expression of MHC molecules and inflammatory cytokines and cell aggregation genes) and simultaneously increases their immunosuppressive activity by upregulating IDO1. Taken together, our newly established MSC priming method may contribute to MSC-based cell therapy for inflammatory diseases.

Varicella zoster-associated progressive lower cranial and upper cervical polyneuropathy: a case report.

BACKGROUND: Multiple cranial neuropathies carry a wide range of differential diagnoses, and when combined with cerebrospinal fluid monocytosis they often suggest an infective etiology. Reactivation of varicella zoster virus has been associated with a wide range of neurological complications. Among the cranial nerves, the upper cranial nerves (trigeminal and facial nerves) are more commonly affected; there have been some reports of lower cranial polyneuropathies resulting from varicella zoster virus reactivation. However, polyneuropathy involving both the cranial and cervical nerves is rarely reported. CASE PRESENTATION: This report highlights the case of a 64-year-old Chinese man presenting with an acute, severe dysphagia and dysphonia secondary to herpes zoster-associated progressive polyneuropathy involving the lower cranial and upper cervical nerves, without any mucocutaneous manifestations. CONCLUSIONS: To our knowledge, this is the first case of varicella zoster virus-associated cranial and cervical polyneuropathy in the literature. The report also highlights the poor sensitivity of varicella zoster virus DNA detection by polymerase chain reaction in the cerebrospinal fluid, and proposes that serology be routinely performed in such polymerase chain reaction-negative cases without a clear diagnosis.

Recommendations for clinical interpretation of variants found in non-coding regions of the genome.

BACKGROUND: The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts. METHODS: We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups. RESULTS: We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants. CONCLUSIONS: These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.

Recommendations for reporting results of diagnostic genomic testing.

Results of clinical genomic testing must be reported in a clear, concise format to ensure they are understandable and interpretable. It is important laboratories are aware of the information which is essential to make sure the results are not open to misinterpretation. As genomic testing has continued to evolve over the past decade, the European Society of Human Genetics (ESHG) recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic) published in 2014 have been reviewed and updated to provide the genomic community with guidance on reporting unambiguous results.

Aryl hydrocarbon receptor-targeted therapy for CD4+ T cell-mediated idiopathic pneumonia syndrome in mice.

We previously demonstrated that interferon γ (IFN-γ) derived from donor T cells co-opts the indoleamine 2,3-dioxygenase 1 (IDO1) → aryl hydrocarbon receptor (AHR) axis to suppress idiopathic pneumonia syndrome (IPS). Here we report that the dysregulated expression of AP-1 family genes in Ahr-/- lung epithelial cells exacerbated IPS in allogeneic bone marrow transplantation settings. AHR repressed transcription of Jund by preventing STAT1 from binding to its promoter. As a consequence, decreased interleukin-6 impaired the differentiation of CD4+ T cells toward Th17 cells. IFN-γ- and IDO1-independent induction of Ahr expression indicated that the AHR agonist might be a better therapeutic target for IPS than the IDO1 activator. We developed a novel synthetic AHR agonist (referred to here as PB502) that potently inhibits Jund expression. PB502 was highly effective at inducing AHR activation and ameliorating IPS. Notably, PB502 was by far superior to the endogenous AHR ligand, L-kynurenine, in promoting the differentiation of both mouse and human FoxP3+ regulatory CD4+ T cells. Our results suggest that the IDO1-AHR axis in lung epithelial cells is associated with IPS repression. A specific AHR agonist may exhibit therapeutic activity against inflammatory and autoimmune diseases by promoting regulatory T-cell differentiation.

Unstable Pathologic Vertebral Fractures in Multiple Myeloma : Propensity Score Matched Cohort Study between Reconstructive Surgery with Adjuvant Radiotherapy and Radiotherapy Alone.

OBJECTIVE: Although radiotherapy (RT) is recommended for multiple myeloma (MM) involving spine, the treatment of choice between reconstructive surgery with RT and RT alone for pathologic vertebral fractures (PVFs) associated with structural instability or neurologic compromises remains controversial. The purpose of this study was to evaluate the clinical efficacies of reconstructive surgery with adjuvant RT for treatment of MM with PVFs by comparing with matched cohorts treated with RT alone. METHODS: Twenty-eight patients underwent reconstructive surgery followed by RT between 2008 and 2015 in a single institution, for management of PVFs associated with structural instability of the spine and/or neurologic compromises (group I). Twentyeight patients were treated with RT alone (group II) after propensity score matching in a 1-to-1 format based on instability of the spine, as well as age and performance. Clinical outcomes including the overall survival rates, duration of independent ambulation, neurological status, and numeric rating scale (NRS) for back pain were compared. RESULTS: Clinical and radiological features before treatment were similar in both groups. The median survival period was similar between the two groups. However, the mean duration of independent ambulation was significantly longer in group I (88.8 months; 95% confidence interval [CI], 66.0-111.5) than in group II (39.4 months; 95% CI, 25.2-53.6) (log rank test; p=0.022). Deterioration of Frankel grade (21.4% vs. 60.7%, p=0.024) and NRS for back pain (2.7±2.2 vs. 5.0±2.7, p=0.000) at the last follow-up were higher in the group II. Treatment-related complications were similar in both groups. CONCLUSION: In patients with unstable PVFs due to MM, reconstructive surgery may yield superior clinical outcomes compared with RT alone in maintaining independent ambulation and neurological status, as well as pain control despite similar median survival and complications.

Establishment of geochemical thresholds for vanadium throughout Korea and at potential development sites using geochemical map data.

Geochemical maps can be used for a variety of purposes, one of which is to establish regional or local geochemical thresholds for the analyzed elements. In the case of vanadium, as industrial demand and use increase, it is necessary to expand the development of vanadium in Korea. However, the environmental management standards are insufficient. Therefore, in this study, using geochemical data, we derived geochemical threshold values for the entire country and areas with potential for the development of vanadium deposits. The regional (country-wide) threshold value was derived using logarithmic transformation of raw data (N = 23,548) of the first- and second-order stream sediments collected across the country in the late 1990s and the early 2000s. The median + 2 median absolute deviation (MAD) and Tukey inner fence (TIF) values were 116 mg/kg and 200 mg/kg, respectively. Of these, the TIF standard, which showed 0.6% of data exceeding the threshold, was judged to be appropriate for distinguishing clear enrichment or contamination of vanadium. In the case of the Geumsan and Pocheon, areas with potential for vanadium development, the TIF and median + 2 MAD values of 259 mg/kg and 218 mg/kg, respectively, can be used as the criteria for evaluating the impact of environmental pollution before and after deposit development. Likewise, by deriving threshold values of the target elements using geochemical map data, it is possible to provide basic environmental information for geochemical evaluation and follow-up management in advance during large-scale site development.

Automated reanalysis application to assist in detecting novel gene-disease associations after genome sequencing.

PURPOSE: This study aimed to investigate whether a bioinformatics application can streamline genome reanalysis and yield new diagnoses for patients with rare diseases. METHODS: We developed TierUp to identify variants in new disease genes for unresolved rare disease cases recruited to the 100,000 Genomes Project, all of whom underwent genome sequencing. TierUp uses the NHS Genomic Medicine Service bioinformatics infrastructure by securely accessing case details from the Clinical Interpretation Portal application programming interface and by querying the curated PanelApp database for novel gene-disease associations. We applied TierUp to 948 cases, and a subset of variants were reclassified according to the American College of Medical Genetics and Genomics/Association of Molecular Pathology guidelines. RESULTS: A rare form of spondylometaphyseal dysplasia was diagnosed through TierUp reanalysis, and an additional 4 variants have been reported to date. From a total of 564,441 variants across patients, TierUp highlighted 410 variants present in novel disease genes in under 77 minutes, successfully expediting an important reanalysis strategy. CONCLUSION: TierUp supports claims that automation can reduce the time taken to reanalyze variants and increase the diagnostic yield from molecular testing. Clinical services should leverage bioinformatics expertise to develop tools that enable routine reanalysis. In addition, services must also explore the ethical, legal, and health economic considerations raised by automation.

Automated reanalysis, a novel way to diagnose an ultra-rare condition: Fibronectin-1-related spondylometaphyseal dysplasia (SMD-FN1).

We report a further case of spondylometaphyseal dysplasia - corner fracture type due to the fibronectin-1 gene (SMD-FN1) in a child originally thought to have metaphyseal chondrodysplasia-Brussels type (MCD Brussels). We highlight phenotypic differences with the SMD-FN1 published reports. This case is unique in terms of the method of molecular confirmation. Findings from the 100 000 Genomes Project were originally negative (in both tier 1 and 2); however, subsequent reanalysis, initiated by an automated search for new gene-disease associations in PanelApp, highlighted a candidate diagnostic variant. Our child had short stature, facial dysmorphism, spondylometaphyseal dysplasia and corner fractures and a heterozygous de novo missense variant in FN1 (c.675C>G p.(Cys225Trp), which was likely pathogenic. The variant matched the clinical and radiological features and a diagnosis of SMD-FN1 was confirmed. We explore the diagnostic journey of this patient, compare her findings with the previous 15 patients reported with SMD-FN1 and discuss the diagnostic utility of automated reanalysis. We consider differences and similarities between MCD Brussels and SMD-FN1, by reviewing literature on both conditions and assess whether they are in fact the same disorder.

A hemizygous mutation in the FOXP3 gene (IPEX syndrome) resulting in recurrent X-linked fetal hydrops: a case report.

BACKGROUND: Fetal hydrops is excessive extravasation of fluid into the third space in a fetus, which could be due to a wide differential of underlying pathology. IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome primarily affects males. It is a monogenic primary immunodeficiency syndrome of X-linked recessive inheritance due to FOXP3 gene variants. It is characterised by the development of multiple autoimmune disorders in affected individuals. CASE PRESENTATION: We present a rare cause of male fetal hydrops in the context of IPEX syndrome and discuss FOXP3 gene variants as a differential for 'unexplained' fetal hydrops that may present after the first trimester. DISCUSSION AND CONCLUSIONS: In all similar cases, the pathological process begins during intrauterine life. Furthermore, there are no survivors described. Consequently, this variant should be considered as a severe one, associated with intrauterine life onset and fatal course, i.e., the most severe IPEX phenotype.

Aging effects on fractionation and speciation of redox-sensitive metals in artificially contaminated soil.

Artificially contaminated soil is often used in laboratory experiments as a substitute for actual field contaminated soils. In the preparation and use of laboratory contaminated soils, questions remain as to how much and how long metals remain in labile form and in their oxidation state during the contamination process. Therefore, the objectives of this study were to determine if the speciation of added contaminants can be retained in the original form and to observe the change in lability of each element with aging time. In this study, natural soil was artificially polluted with five redox-sensitive toxic elements in their oxidized or reduced forms, i.e., As(III)/As(V), Sb(III)/Sb(V), Cr(III)/Cr(VI), Mo(VI), and W(V). Metal distribution was measured in progressive chemical fractionation using sequential extraction methods in contaminated soils after 3, 100, and 300 days of aging. The results indicated that the more strongly bound fraction of metals increased by day 100; whereas the fractions were not significantly different from those in the 300-day-aged soil. Among five metals, the ratio of weakly-bound fractions remained highest in As- and lowest in Cr-contaminated soils. The W(VI)-contaminated soil showed strong sorption without changes in speciation during aging. The oxidized or reduced metal species converged to occur as a single species under given soil conditions, regardless of the initial form of metal used to spike the soil. Both As and Sb existed as their oxidized form while Cr existed as its reduced form. The results of this study may provide a useful and practical guideline for artificial soil contamination.

Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity.

OBJECTIVE: Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1). DESIGN AND METHODS: Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions. RESULTS: Both cohorts were enriched for class 3-5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts. CONCLUSIONS: Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.

No association between POU4F1, POU4F2, ISL1 polymorphisms and normal-tension glaucoma.

BACKGROUND: Normal-tension glaucoma (NTG) that occurs despite normal intraocular pressure has genetic predisposition. Since retinal ganglion cells (RGCs) are a key node in pathogenesis of glaucoma, neurodegeneration of RGCs is thought to be the main cause increasing the risk of NTG development. Here, we aimed to investigate the association of polymorphisms in RGC development genes with NTG development. MATERIALS AND METHODS: We performed a case-control association study of 435 patients with NTG and 419 normal controls. We genotyped four single nucleotide polymorphisms (SNPs) in genes responsible for RGC development, namely POU4F2 (rs13152799 and rs1504360), POU4F1 (rs9601092), and ISL1 (rs2288468), by either real-time PCR or PCR-RFLP, and evaluated its association with the risk of NTG development. RESULTS: No significant association was observed between the candidate SNPs and NTG development. CONCLUSIONS: To the best of our knowledge, this is the first report exploring the association between genes regulating RGC development and NTG susceptibility. Our data could provide a reference for further researches that focus on finding additional potential SNPs of POU4F2, POU4F1, ISL1 or other RGC development genes for NTG.

Effect of FeS on mercury behavior in mercury-contaminated stream sediment: A case study of Pohang Gumu Creek in South Korea.

This study investigated mercury contamination with respect to the sediment characteristics in Gumu Creek near the Pohang Industrial Complex, South Korea. The contaminated sediment had high levels of Hg, exceeding 250 mg Hg/kg sediment at the sampling position, and high concentrations of iron, sulfur, and organic carbon under extreme anaerobic conditions. The anoxic condition of the sediment produced large amounts of FeS. Hg L3-edge EXAFS analysis revealed that FeS controlled the Hg species in the sediment mainly as ß-HgS like precipitation or Hg-S complexation. We also speculated that the presence of FeS induced the abiotic reduction of Hg(II) to Hg(0) and consequently suppressed the formation of highly toxic methylated mercury species. The results obtained in this study are mostly consistent with those reported in previous studies of geochemical reactions of FeS in controlling Hg(II) under pure FeS mineral systems under laboratory scenarios. This study demonstrates that the laboratory controlled reaction scenarios can explain the field behavior of Hg in the contaminated anoxic sediment of the Gumu Creek site.

A novel non-invasive prenatal sickle cell disease test for all at-risk pregnancies.

Sickle cell disease (SCD) is the most common genetic haematological disorder. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived procedure-related miscarriage risk. We report the development of a targeted massively parallel sequencing (MPS) assay for the NIPD of fetal SCD using fetal cell-free (cf)DNA from maternal plasma, with no requirement for paternal or proband samples. In all, 64 plasma samples from pregnant women were analysed: 42 from SCD carriers, 15 from women with homozygous (Hb SS) SCD and seven from women with compound heterozygous (Hb SC) SCD. Our assay incorporated a relative mutation dosage assay for maternal carriers and a wild type allele detection assay for affected women (Hb SS/Hb SC). Selective analysis of only smaller cfDNA fragments and modifications to DNA fragment hybridisation capture improved diagnostic accuracy. Clinical sensitivity was 100% and clinical specificity was 100%. One sample with a fetal fraction of <4% was correctly called as 'unaffected', but with a discordant genotype (Hb AA rather than Hb AS). Six samples gave inconclusive results, of which two had a fetal fraction of <4%. This study demonstrates that NIPD for SCD is approaching clinical utility.

Genomic Characterization of TBK1 Duplication in Korean Normal-tension Glaucoma Patients.

PRéCIS:: One (0.2%) of 418 Korean normal-tension glaucoma (NTG) patients had TBK1 duplication. The putative mechanism of TBK1 duplication in Korean NTG patients is the nonhomologous end-joining. PURPOSE: TBK1 duplication is a genomic cause of familial NTG. NTG accounts for up to 90% of primary open-angle glaucoma in Koreans, with genetic tendency. We aimed to investigate the prevalence of TBK1 duplication in Korean NTG patients and to identify their genomic structure and duplication mechanism. MATERIALS AND METHODS: We obtained DNA samples from 418 NTG patients and 195 healthy controls for evaluating TBK1 copy number variations using a semiquantitative polymerase chain reaction (PCR). The samples with TBK1 gene duplication were further confirmed using droplet digital PCR. The whole-genome sequencing of patient samples with duplications was performed to identify the accurate breakpoints and to elucidate the genomic structure. Ophthalmic evaluation and confirmation of TBK1 duplication using junction PCR were performed in families of positive patients. RESULTS: TBK1 duplication was found in 1 of 418 NTG cases (0.2%). The duplication range was from g.64,803,151 to g.64,927,214 (124,063 bp). It is the smallest region of overlapping duplication in TBK1. Any repetitive sequences were not found near the breakpoints of our case. Inserted sequences were found within the breakpoints. A brother and a niece of the positive case appeared the typical clinical features of NTG and shared the same TBK1 duplications with the index case. CONCLUSIONS: In Korea, the prevalence of TBK1 duplication was 0.2% and the smallest reported TBK1 duplication associated with NTG was found. The mechanism of TBK1 duplication was suggested to be nonhomologous end-joining while a previous report pointed out the mechanism of TBK1 duplications as nonallelic homologous recombination.

Redox transformation of soil minerals and arsenic in arsenic-contaminated soil under cycling redox conditions.

Changes in the saturation degree of aquifers control the geochemical reactions of redox-sensitive elements such as iron (Fe), sulfur (S), and arsenic (As). In this study, the effects of redox conditions and the presence of Fe and S on the behavior of As in a soil environment were investigated by observation in a batch experimental system. Arsenic was stable on Fe(III) solid surface in an oxidizing environment but was easily released into the aqueous phase following the reductive dissolution of Fe during an anoxic period. The alternating redox cycles led to a change in the concentrations of Fe, S, and As in both the aqueous and solid phases. The composition of Fe minerals changed to a less crystalline phase while that of solid phase As changed to a more reduced phase in both the As-contaminated natural soil and FeS-amended soil batch systems. This tendency was more prominent in the batch containing higher amounts of total Fe and S. These results show that a redox cycle can increase the possibility of As contamination of groundwater during dissolution and reprecipitation of Fe minerals and simultaneous microbial reduction of S and/or As species.

Sphingorhabdus pulchriflava sp. nov., isolated from a river.

A facultatively anaerobic and Gram-stain-negative bacterium, strain GY_GT, was isolated from a river (Daedeock-cheon) in Daejeon, Republic of Korea. The isolate was catalase-positive, oxidase-positive and formed yellow colonies. Strain GY_GT was phylogenetically classified as belonging in the genus Sphingorhabdus. Its closely related strains were Sphingorhabdus wooponensis 03SU3-PT (97.1 % similarity), Sphingorhabdus buctiana T5T (96.9 %), Sphingorhabdus contaminans JC216T (96.5 %), Sphingorhabdus rigui 01SU5-PT (96.5 %) and Sphingorhabdus planktonica G1A_585T (96.3 %) based on 16S rRNA gene sequences. The growth conditions for GY_GT were at 10-45 °C (optimum, 25 °C), pH 6-10 (pH 7) and 0-4% NaCl (0.5-1.5 %). Strain GY_GT could utilize turanose, d-fructose-6-phosphate, glucuronamide, α-keto-glutaric acid and acetoacetic acid. The major fatty acids of strain GY_GT were summed features 8 (C18 : 1 ω7c/C18 : 1 ω6c; 40.6 %) and 3 (C16 : 1 ω6c/C16 : 1 ω7c; 24.7 %). The major quinone required for respiration was Q-10. The polar lipids of strain GY_GT were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and sphingolipid. The G+C content of the genome was 57.7 mol%. The average nucleotide identity and average amino acid identity values between strains GY_GT and S. wooponensis were 71.0 and 72.7 %, respectively. Based on phylogenetic and phenotypic attributes, we suggest that strain GY_GT is a novel species in the genus Sphingorhabdus and propose the name Sphingorhabdus pulchriflava. The type strain is GY_GT (=KCTC 62791T=JCM 32855T).

Structural Aberrations with Secondary Implications (SASIs): consensus recommendations for reporting of cancer susceptibility genes identified during analysis of Copy Number Variants (CNVs).

Clinical testing with chromosomal microarray (CMA) is most commonly undertaken for clinical indications such as intellectual disability, dysmorphic features and/or congenital abnormalities. Identification of a structural aberration (SA) involving a cancer susceptibility gene (CSG) constitutes a type of incidental or secondary finding. Laboratory reporting, risk communication and clinical management of these structural aberrations with secondary implications (SASIs) is currently inconsistent. We undertake meta-analysis of 18 622 instances of CMA performed for unrelated indications in which 106 SASIs are identified involving in total 40 different CSGs. Here we present the recommendations of a joint UK working group representing the British Society of Genomic Medicine, UK Cancer Genetics Group and UK Association for Clinical Genomic Science. SASIs are categorised into four groups, defined by the type of SA and the cancer risk. For each group, recommendations are provided regarding reflex parental testing and cancer risk management.