Magnitude and Impact of Workplace Violence Against Obstetric Healthcare Personnel: A Multicentre Cross-Sectional Study.

Background: Workplace violence is defined by the World Health Organization (WHO) as incidents where staff is abused, threatened or assaulted in work settings. In emergency predominated branch like obstetrics, there is a need to study the magnitude and impact of violence against healthcare workers (HCW). Materials and Methodology: This cross-sectional study was conducted in the Department of Obstetrics at 2 centres in Lucknow district, for a period of 6 months. The study population included trainee residents, senior residents, nursing staff and consultants. Standard definitions from the WHO were used to define the types of violence. The validated questionnaire was designed in English with 25 questions to understand the incidence of workplace violence, prevention policy, reporting and follow-ups of incidents and impact of violence. Results: With a response rate of 90%, 274 HCW participated in the study. In total, 172 HCW (62.7%) either faced physical or verbal assault. In 70% of incidents, patient, their relatives or public were perpetrators of violence, and the rest 30% incidents were by colleagues or management. Majority of the incidents were in emergency areas. Only 22% of the abused reported to the concerned authorities. At least 123 (71.5%) HCW were extremely dissatisfied with the action taken. Action was taken against only 9.8% of the perpetrators. None of the respondents received any training to handle workplace violence. Conclusion: There is an alarming high prevalence of workplace violence by patients and colleagues. Adequate training to handle these incidents, improvement of working environment and unconditional support from management will bring a positive work experience. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-023-01809-0.

Correlation of sFlt/PlGF ratio with severity of preeclampsia in an Indian population.

Background: Preeclampsia affects 2% to 8% of pregnant women and significantly increases the risk for maternal and perinatal morbidity, especially in low- and middle-income countries. There is increasing evidence to support the use of biochemical markers such as placental growth factor and soluble fms-like tyrosine kinase-1 in predicting the severity of preeclampsia and to rule out severe disease in clinical conditions masquerading as severe preeclampsia. OBJECTIVE: This study aimed to assess the role of the sFlt-1/PlGF ratio in predicting adverse perinatal and maternal outcomes in women with preeclampsia in a South Asian population with a higher rate of the disease and its associated complications. STUDY DESIGN: This was a prospective cohort study of women diagnosed with preeclampsia or suspected to have preeclampsia who underwent biophysical and biochemical investigations to measure the severity, including determining maternal hemodynamic indices, mean arterial pressure, fetal biometric and Doppler parameters, and soluble fms-like tyrosine kinase-1 and placental growth factor levels. The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver operating characteristic curve analysis. An adverse maternal outcome was defined as 1 or more of severe hypertension; admission to the intensive care unit; eclampsia; placental abruption; hemolysis, elevated liver enzymes, low-platelet count syndrome; disseminated intravascular coagulation; platelets <100×109/L; creatinine >1.1 mg/dL; and alanine aminotransferase >100 U/L. An adverse perinatal outcome was defined as 1 or more of preterm birth ≤34+0 weeks' gestation, neonatal intensive care unit admission for >48 hours, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity, and confirmed fetal infection. RESULTS: We recruited 91 women with preeclampsia with a mean gestational age of 30.63±2.86 weeks. Women who had adverse maternal events had higher median maternal concentrations of soluble fms-like tyrosine kinase (11,500.0 pg/mL vs 3051.0 pg/mL; P<.001), lower concentrations of placental growth factor (44.88 pg/mL vs 148.50 pg/mL; P<.001), and a higher sFlt-1/PlGF ratio (306.22 vs 30.63; P<.001) than women who did not. Pregnancies with an adverse perinatal outcome also had a higher soluble fms-like tyrosine kinase concentration (12,100.0 pg/mL vs 3051.0 pg/mL; P<.001), lower placental growth factor concentration (27.2 pg/mL vs 148.50 pg/mL; P<.001), and higher sFlt-1/PlGF ratio (378.45.4 vs 30.63; P<.001). The area under the receiver operating characteristic curve showed that soluble fms-like tyrosine kinase and placental growth factor were the best biomarkers when compared with other biochemical markers to predict adverse maternal (area under the curve, 0.81; 95% confidence interval, 0.72-0.90) and fetal (area under the curve, 0.88; 95% confidence interval, 0.80-0.96) outcomes in preeclampsia. CONCLUSION: The sFlt-1/PlGF ratio correlates better with adverse maternal and perinatal outcomes than any other biochemical marker in an Indian population. The incorporation of the sFlt-1/PlGF ratio in women with preeclampsia can help in predicting the severity of the condition and the timings of the delivery.

Obstetric outcomes in pregnant women with subacute sclerosing panencephalitis (SSPE): a systematic review of case reports and case series.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a devastating brain disease caused by persistent infection by the measles virus. Several cases of SSPE in pregnant ladies have been described. This systematic review is focused on maternal and foetal outcomes among pregnant women with SSPE. METHODS: We searched four databases (PubMed, Embase, Scopus, and Google Scholar). We reviewed all relevant cases, published until 14 August 2022. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered with PROSPERO (CRD42022348630). The search items that we used were "((Pregnancy) OR (delivery)) AND (Subacute sclerosing panencephalitis (SSPE))". Dyken's criteria were used for the diagnosis of SSPE in pregnant women. The extracted data was recorded in an Excel sheet. The Joanna Briggs Institute Critical Appraisal tool for case reports was used to assess the quality of published cases. RESULTS: We came across 19 reports describing details of 21 cases. The age of SSPE-affected women varied from 14 to 34 years (mean 23 years). In the majority (n=14), clinical manifestations were started in the antepartum period. Nine pregnant SSPE women presented with vision loss. After delivery, 13 SSPE-affected women died. On the contrary, 15 foetuses, though the majority were preterm, were alive. Five foetuses either died soon after birth or were still-born. CONCLUSION: In conclusion, SSPE in pregnancy is often missed, as it mimics eclampsia. SSPE in pregnancy usually has a devastating course. Universal early childhood measles vaccination is the only way to fight this menace.

Comparison of frequency domain parameters of heart rate variability between women with polycystic ovarian disease and apparently healthy women.

Background: Polycystic ovary syndrome (PCOS) patients shows common features like increased insulin resistance and adiposity, which have been known to correlate with sympathetic hyperactivity. Objective: The aim of this study is to analyze the characteristics of heart rate variability in women with PCOS. To compare frequency domain parameters of heart rate variability (HRV) between women with PCOS and apparently healthy women. To study the impact of cardiometabolic parameters such as BMI and blood pressure on frequency-domain HRV parameters. Methods: A total of 30 women with PCOS aged 20 to 40 years (as per Rotterdam criteria) were enrolled as cases and 30 age-matched women having normal ovulatory cycles were enrolled as controls. HRV was recorded using an electrocardiography machine (ECG) machine. The following frequency-domain parameters were assessed: Total power, Very low frequency (VLF), VLF%, Low Frequency (LF), LF%, LF nu, High frequency (HF), HF%, HF nu, LF/HF ratio, short-term variability (SD1), and long-term variability (SD2), respectively. Results: Mean age of cases was 28.03 ± 5.33 years. Mean BMI of PCOS women was 25.39 ± 2.69 kg/m2. A total of 18 (60%) had BMI >25 kg/m2. Cases had significantly higher BMI, waist hip ratio, and blood pressure as compared with controls. None of the controls had BMI >25 kg/m2. Majority of cases (66.7%) had systolic blood pressure/diastolic blood pressure (SBP/DBP) >130/85 mmHg as compared with only 6 (20%) of controls (P < 0.001). For different frequency domain parameters, no statistically significant difference between two groups was observed for VLF and LF. Mean VLF%, LF%, LF (nu), and LF/HF were significantly higher in cases as compared with controls. For all, the other mean value was significantly lower in cases as compared with that of controls (P < 0.05). Conclusions: Autonomic nervous system is affected by PCOS status of women, and sympathetic hyperactivity is seen.

Association of long and short interpregnancy intervals with maternal outcomes.

Background: Interpregnancy interval (IPI) is spacing between live birth and beginning a new pregnancy. Both long and short IPIs have been associated with adverse maternal outcomes. There is paucity in the Indian literature regarding the impact of IPI on maternal outcomes. Materials and Methodology: The cross-sectional study was conducted in the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, from July 2019 to June 2020. Women with previous abortions, previous stillbirth, nulliparity, or multiple pregnancies were excluded. A pre-structured pro forma was used for demographic details. IPI was categorized as <6 months, 6 to <24 months, 24 to <60 months, and 60 months. Maternal outcomes were studied, and odds ratios were calculated. Results: There were 6984 deliveries in the period. A total of 4812 women were enrolled after following the inclusion and exclusion criteria. Of 4812 women, 142 (2.9%) had IPI <6 months, 3336/4812 women (69.3%) had IPI 6 to <24 months, 1144/4812 women (23.7%) had IPI 24 to <60 months, and 3.9% women (190/4812) had IPI ≥60 months. High risk of fetal malposition (OR 3.84), fetal growth restriction (OR 2.06), and hypertension (OR 1.86) were seen in women with short IPI <6 months. Women with longer IPI (≥ 60 months) had higher chances of preterm labor (OR 3.82), oligoamnios (OR 2.54), gestational diabetes (OR 2.19), and anemia (OR 1.45). Conclusion: Three-fourths of women had IPI less than 24 months recommended as minimum interval by WHO. Efforts are needed to increase awareness and availability of contraceptive choices for postpartum women to ensure adequate spacing.

Vaginal probiotics as an adjunct to antibiotic prophylaxis in the management of preterm premature rupture of the membranes.

Preterm birth is a leading cause of perinatal morbidity and mortality and Preterm premature rupture of the membranes (PPROM) is a major risk factor contributing to approximately one third of preterm deliveries. Vaginal infections are often associated with PPROM and are characterised by loss of lactobacillin normal vaginal flora and overgrowth of other pathogenic microorganisms. Probiotics appear to have an emerging role in prolonging pregnancy after PPROM. This trial compared the efficacy of a vaginal probiotic in combination with standard antibiotic prophylaxis versus only antibiotic in prolongation of latency period and on perinatal outcome in cases of PPROM between 24 and 34 weeks. Although no significant difference was observed in the mean latency period (p = 0.937) and mean gestational age at birth (p = 0.863) between the two groups, the overall neonatal outcome was better in the study group. There is need of further large-scale clinical trials to demonstrate effectiveness of probiotics.IMPACT STATEMENTWhat is already known on this subject? PPROM is an important cause of preterm birth. Prematurity leads significant global burden of neonatal morbidity and mortality. Antibiotics in PPROM have a proven benefit to prolong latency period from start of PPROM to birth. Probiotics have a role in improving vaginal flora and reducing infections and have been tried in PPROM.What do the results of this study add? The usefulness of probiotics in prolonging latency period and improving neonatal outcome has been reported in limited trials. In our study it has shown an improvement in neonatal outcome overall but not statistically significant compared to few studies which have reported significant beneficial effects. This might be due to existence of variation in the type of the vaginal microflora in different study population.What are the implications of these findings for clinical practice and/or further research? Preliminary results suggest that use of probiotic may benefit women with PPROM. This also implies need of multicentric larger scales trials with different types of probiotics so as to clarify whether any intervention in vaginal microflora can lead to any benefits in reducing the prematurity and its consequence, both on the neonate and heath care infrastructure.

A novel resource management technique for deadlock-free systems.

Deadlock in a shared resource system is a well-known problem. It has been extensively studied and recently a new class of resource reservation technique is researched upon for deadlock free resource management. This class of technique reserves a portion of the resources. The unreserved resources are freely allocated to any process demanding it. When the unreserved resources are not sufficient for a process demand the reserve pool resources are used such that the process completes and releases all the resources it is holding. This paper presents a new resource reservation technique resource driven DFRR. This technique estimates the optimal number of resources needed for a deadlock free resource reservation policy. The correctness is proved in the form of theorem 1. The theorem 2, suggests the resource reservation with minimal resources. The overhead of the resource pool estimation is O n and that of resource management is O m which is optimal for any deadlock handling technique. The effectiveness of the proposed technique is shown in the form of examples and simulation results.

Limited role of GeneXpert in peritoneal fluid in the diagnosis of genital tuberculosis in infertile women.

BACKGROUND AND OBJECTIVES: Genital tuberculosis (TB) is an important cause of infertility in women that poses many challenges in diagnosis. The study is done to understand the utility of GeneXpert test in peritoneal fluid in the diagnosis of genital TB in infertile women. METHODS: All infertile women in postmenstrual phase who were planned for laparoscopy in study period were included. Women who were already on anti-TB therapy were excluded. Peritoneal fluid/washings were retrieved during laparoscopy to test for Mycobacterium tuberculosis by GeneXpert. A note was made of laparoscopy evidence of TB. Endometrial sample was sent for microbiological testing of mycobacterium on smear and liquid culture. Histopathological test of endometrium was also done to look for granulomas. RESULTS: In a total of 57 women, 8 (14.03%) women were diagnosed with TB on the basis of laparoscopy or microbiological or histopathological tests. Six women had caseating tubercles in pelvis, of them two women had presence of mycobacterium on smear, one woman also had positive liquid culture. In two women endometrial smear was positive. None of the women had a positive GeneXpert test in peritoneal fluid. CONCLUSION: Genital TB is a clinical problem in infertile women. Even in women with confirmed genital TB the peritoneal fluid/washings were negative for mycobacterium. GeneXpert did not pick Mycobacterium in peritoneal fluid in women with genital TB. Hence, it is not a sensitive and good tool for the diagnosis of female genital TB.

Pregnancy in women with previous two healthy children, associated factors, and acceptability of contraception among these women: A questionnaire-based, cross-sectional KAP study in world's second most populated country advocating two-child norm.

INTRODUCTION: Indian subcontinent carries 17 % of world's population, being the second largest populated country. The maternal mortality rate of the country is still high. The study was aimed to study factors leading to pregnancy in women with previous two living children and their knowledge about limiting family and their practice for use of contraceptives. METHODS: Questionnaire-based study was conducted in the Department of Obstetrics and Gynaecology. RESULTS: 961 pregnant women attending antenatal outpatient department were interrogated and amongst them 167 (17.3 %) multigravida with previous two healthy children were enrolled in study and were asked to document in Questionnaire. Reasons for current pregnancy were gender bias, no desire to limit family, incorrect contraceptive use, contraceptive failure, doctor's mistake and religious belief. Desire for male child emerged as most common reason (37%) followed by improper or no use of contraception. Most significant associated factor was poor education of female partner (p = 0.010). CONCLUSION: This cross-sectional study evaluated the possible reasons of multiparity. We conclude that preference for male gender child is still very much prevalent in India, along with unmet need of family planning. Improving education of women might help to change attitude towards birth spacing and family size.

Pilot Interventional Study Comparing Fetomaternal Outcomes of 150 mg Versus 75 mg Aspirin Starting Between 11 and 14 Weeks of Pregnancy in Patients with High Risk of Preeclampsia: A Randomized Control Trial.

INTRODUCTION: Hypertensive disorders of pregnancies complicate around 5-10% of pregnancies worldwide, and together they are a member of the deadly triad along with haemorrhage and infection that contribute to a significant amount of maternal morbidity and mortality. AIMS AND OBJECTIVES: To compare differences in the fetomaternal outcomes with the use of 150 mg aspirin versus 75 mg aspirin in pregnant women found to be at high risk of PE. METHODOLOGY: This was a two-armed double-blind parallel randomized control trial conducted in the Department of Obstetrics and Gynaecology, King George's Medical University, carried over a period of 1 year. RESULTS: Preeclampsia occurred in 15 of 87 participants (17%) in the 75 mg aspirin group compared with 6 of 91 (6.5%) in the 150 mg aspirin group. There were a significantly higher incidence of PE, its severity and lesser period of gestation at delivery in the group given 75 mg dose compared to the group given 150 mg dose. There were significantly higher values of mean arterial pressure and uterine artery PI in women who developed preeclampsia compared to those who do not in both the groups. Foetal outcomes were observed in both the groups of women, and there was no statistically significant difference between them. CONCLUSION: This randomized trial showed that among women with singleton pregnancies who were identified by means of first-trimester screening as being at high risk of preterm preeclampsia, use of aspirin 150 mg per day started between 11 and 14 weeks till 36 weeks is a potent intervention to reduce the development of both early- and late-onset preeclampsia as compared to a dose of 75 mg per day.

Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects.

Mutations in the transcription factor genes FOXE3, HSF4, MAF, and PITX3 cause congenital lens defects including cataracts that may be accompanied by defects in other components of the eye or in nonocular tissues. We comprehensively describe here all the variants in FOXE3, HSF4, MAF, and PITX3 genes linked to human developmental defects. A total of 52 variants for FOXE3, 18 variants for HSF4, 20 variants for MAF, and 19 variants for PITX3 identified so far in isolated cases or within families are documented. This effort reveals FOXE3, HSF4, MAF, and PITX3 to have 33, 16, 18, and 7 unique causal mutations, respectively. Loss-of-function mutant animals for these genes have served to model the pathobiology of the associated human defects, and we discuss the currently known molecular function of these genes, particularly with emphasis on their role in ocular development. Finally, we make the detailed FOXE3, HSF4, MAF, and PITX3 variant information available in the Leiden Online Variation Database (LOVD) platform at https://www.LOVD.nl/FOXE3, https://www.LOVD.nl/HSF4, https://www.LOVD.nl/MAF, and https://www.LOVD.nl/PITX3. Thus, this article informs on key variants in transcription factor genes linked to cataract, aphakia, corneal opacity, glaucoma, microcornea, microphthalmia, anterior segment mesenchymal dysgenesis, and Ayme-Gripp syndrome, and facilitates their access through Web-based databases.

Torsion and rupture of a non-communicating rudimentary horn in a 17-week gestation in a 16-year-old girl: lessons learnt.

A unicornuate uterus with non-communicating rudimentary horn has always been notorious and poses threat to continuation of pregnancy with dismal consequences. We are reporting an interesting case of uterine malformation with a 90° rotation of uterine axis which ultimately ruptured during termination of pregnancy. The rarity in our case was not only conception in non-communicating horn but also the complete twisting of axis which made the pregnant horn come in front of the non-gravid unicornuate uterus, mimicking normal pregnancy. The most important lesson learnt is that if induction does not lead to cervical changes and uterine contractions, one must consider atypical presentations of an anomalous uterus as a possible differential before proceeding further.

Conditional loss of Spata7 in photoreceptors causes progressive retinal degeneration in mice.

The mammalian retina consists of multiple cell layers including photoreceptor cells, which are light sensing neurons that play essential functions in the visual process. Previously, we identified mutations in SPATA7, encoding spermatogenesis associated protein 7, in families with Leber Congenital Amaurosis (LCA) and juvenile Retinitis Pigmentosa (RP), and showed that Spata7 null mice recapitulate the human disease phenotype of retinal degeneration. SPATA7 is expressed in the connecting cilium of photoreceptor (PR) cells in the mouse retina, as well as in retinal pigment epithelium (RPE) cells, but the functional role of Spata7 in the RPE remains unknown. To investigate whether Spata7 is required in PRs, the RPE, or both, we conditionally knocked out Spata7 in photoreceptors and RPE cells using Crx-Cre and Best1-Cre transgenic mouse lines, respectively. In Spata7 photoreceptor-specific conditional (cKO) mice, both rod and cone photoreceptor dysfunction and degeneration is observed, characterized by progressive thinning of the outer nuclear layer and reduced response to light; however, RPE-specific deletion of Spata7 does not impair retinal function or cell survival. Furthermore, our findings show that both Rhodopsin and RPGRIP1 are mislocalized in the Spata7Flox/-; Crx-Cre cKO mice, suggesting that loss of Spata7 in photoreceptors alone can result in altered trafficking of these proteins in the connecting cilium. Together, our findings suggest that loss of Spata7 in photoreceptors alone is sufficient to cause photoreceptor degeneration, but its function in the RPE is not required for photoreceptor survival; therefore, loss of Spata7 in photoreceptors alters both rod and cone function and survival, consistent with the clinical phenotypes observed in LCA and RP patients with mutations in SPATA7.

Fetomaternal outcomes in pregnant women with hepatitis E infection; still an important fetomaternal killer with an unresolved mystery of increased virulence in pregnancy.

OBJECTIVE: Hepatitis is a prevalent infection in developing countries. While hepatitis B and C are deepening their roots in the developed world, hepatitis A and E are common in the developing world. The uniqueness of hepatitis is in its transformation from a relatively self-limiting disease in the non-pregnant state, to a highly virulent disease during pregnancy. MATERIALS AND METHODS: This retrospective observational study was conducted in the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, for a period of six months from June 2016 to November 2016 [probably during an endemic peak of hepatitis E virus (HEV)] to observe the clinical outcomes in HEV-infected pregnant women. RESULTS: A total of 32 anti-HEV immunoglobulin M-positive pregnant women were included, and fetomaternal outcomes were analyzed. Hepatitis E positivity was significantly associated with maternal mortality, intrauterine demise with prematurity, and premature rupture of membranes was the most common fetal complication noted. CONCLUSION: The difference in extent of virulence of infection and variations in maternal morbidity, mortality, and rates of intrauterine demise, signify the presence of some factors that play a role and need to be further studied and evaluated.

REEP6 deficiency leads to retinal degeneration through disruption of ER homeostasis and protein trafficking.

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterize the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localized to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis.

Cervical Pregnancy Masquerading as an Incomplete Abortion- A Learning Lesson.

Cervical pregnancy is a rare site of ectopic pregnancy compared to tubal. The trophoblast implant into the cervical tissue and become a potentially dangerous site of torrential haemorrhage. The widespread use of Ultrasonography (USG) has led to a dramatic increase in the detection rates of extra uterine pregnancy. We hereby report an interesting case of extra uterine pregnancy with a unique situation where only a high index of suspicion prevented an iatrogenic mishap. The patient was referred as a case of incomplete abortion with a documented report of minimal retained products. Because of a high index of suspicion a serum beta Human chorionic gonadotropin (hCG) was sent prior to deciding for discharge. This indeed turned as a major change in the diagnosis of the case as the serum beta hCG was elevated. On re-evaluation, we diagnosed it as a case of cervical pregnancy which was successfully managed medically.

SeqCNV: a novel method for identification of copy number variations in targeted next-generation sequencing data.

BACKGROUND: Targeted next-generation sequencing (NGS) has been widely used as a cost-effective way to identify the genetic basis of human disorders. Copy number variations (CNVs) contribute significantly to human genomic variability, some of which can lead to disease. However, effective detection of CNVs from targeted capture sequencing data remains challenging. RESULTS: Here we present SeqCNV, a novel CNV calling method designed to use capture NGS data. SeqCNV extracts the read depth information and utilizes the maximum penalized likelihood estimation (MPLE) model to identify the copy number ratio and CNV boundary. We applied SeqCNV to both bacterial artificial clone (BAC) and human patient NGS data to identify CNVs. These CNVs were validated by array comparative genomic hybridization (aCGH). CONCLUSIONS: SeqCNV is able to robustly identify CNVs of different size using capture NGS data. Compared with other CNV-calling methods, SeqCNV shows a significant improvement in both sensitivity and specificity.

Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies.

Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network.