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Objective The Automated Neuropsychological Assessment Metrics (ANAM) is a computerized cognitive test system used extensively with military service members. The aim of this study was to develop a nationally representative normative dataset of Army National Guard (ARNG) personnel and to explore potential relationships between ANAM performances and select military service, demographic, and health factors. Methods ANAM performance data were collected using standardized procedures from a representative sample of ARNG service members in six U.S. states. Normative performance values, stratified by age, sex, and military occupational category, were calculated for each ANAM subtest and descriptive measures were computed, along with base rates of below-average performance. The effect of demographic (e.g. age, sex, education, race) and military service and health factors (e.g. deployment, job category, history of head injury) was examined. Results Data from 1,436 ARNG service members (14.3% female) were analyzed, and normative values calculated. Overall, differences in ANAM performance based on demographic, military service, and health factors were small. A total of 8.9% of the sample had scores on two or more subtests that were ≥ 1.3 SD below the mean; this dropped to 1.9% using a more stringent cut point (≥2 SD below the mean). Conclusion The ANAM normative data reported herein ensure that healthcare providers and researchers have access to reference data that more accurately reflect the larger population of ARNG service members. These data support the assessment and management of ARNG service members' health, as well as future ANAM research involving ARNG service members. [ABSTRACT FROM AUTHOR]

Individuals with a family history of alcohol or other substance use disorders (FH+) are at increased risk for developing alcohol and other substance use disorders (AUD/SUD) compared to individuals with no such family histories (FH−). FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH− controls. We hypothesized that family history of AUD/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived from complete blood counts in FH+ (n = 37) and FH− (n = 77) young adults without AUD/SUD to test if immune system dysregulation is present in FH+ individuals. The total WBC count, number of neutrophils and number of monocytes and associated systemic inflammatory response index (SIRI) were significantly increased in the FH+ group. Further, WBC, neutrophil, monocyte counts and SIRI values were all positively correlated with FH density (number of biological parents and grandparents with AUD/SUD). These novel data are the first to identify an association between family history of AUD/SUD and increased circulating leukocytes, which is likely indicative of immune dysregulation in FH+ young adults prior to onset of AUD/SUD. Additional studies are warranted to characterize the functional relevance of the observed immune cell composition in FH+ individuals, but the notion that inexpensive and widely available blood tests may help identify addiction risk could be transformative. [ABSTRACT FROM AUTHOR]

Aim: Hypovitaminosis A is a leading cause of preventable childhood blindness, especially in developing nations. Vitamin A is a fat‐soluble essential micronutrient that serves vital functions in the visual system and in regulating bone resorption. We report on a series of four children with mixed nutritional and compressive optic neuropathy and provide a review of the literature. Methods: A retrospective observational study of four males (ages 9–12), three with autism spectrum disorder who presented with loss of vision and multiple vitamin deficiencies including hypovitaminosis A. Results: Patients presented with unexplained visual loss or a change in visual behaviour. All patients had severely restricted diet comprising of predominantly carbohydrates. Two of the four cases demonstrated optic nerve pallor at initial presentation with marked optic atrophy developing in all patients over time. Electrophysiology available in two patients demonstrated optic nerve dysfunction with preserved retinal function. Extensive investigations revealed profound deficiency in multiple vitamins including vitamin A (<0.1–0.2 μmol/L, normal = 0.9–1.7 μmol/L). Three patients also had low vitamin B12 (90–111 pmol/L, normal = 170–800 pmol/L) with normal folate. All four cases had radiological evidence of skull base thickening indicative of low vitamin A. Genetic testing did not find any relevant pathogenic variants. Conclusions: Hypovitaminosis A is a crucial form of nutritional deprivation that results in significant visual loss with potential hyperostosis and optic nerve compression exacerbating nutritional optic neuropathy. Additional micronutrient deficiencies usually co‐exist and may contribute. Extra vigilance in vitamin replacement is required of clinicians with patients with autism who have restricted diets. [ABSTRACT FROM AUTHOR]

Background: The complexities of mitochondrial disease make epidemiological studies challenging, yet this information is important in understanding the healthcare burden and addressing service and educational needs. Existing studies are limited to quaternary centres or focus on a single genotype or phenotype and estimate disease prevalence at 12.5 per 100 000. New Zealand's (NZ) size and partially integrated national healthcare system make it amenable to a nationwide prevalence study. Aim: To estimate the prevalence of molecularly confirmed and suspected mitochondrial disease on 31 December 2015 in NZ. Methods: Cases were identified from subspecialists and laboratory databases and through interrogation of the Ministry of Health National Minimum Dataset with a focus on presentations between 2000 and 2015. Patient records were reviewed, and those with a diagnosis of 'mitochondrial disease' who were alive and residing in NZ on the prevalence date were included. These were divided into molecularly confirmed and clinically suspected cases. Official NZ estimated resident population data were used to calculate prevalence. Results: Seven hundred twenty‐three unique national health index numbers were identified. Five hundred five were excluded. The minimum combined prevalence for mitochondrial disease was 4.7 per 100 000 (95% confidence interval (CI): 4.1–5.4). The minimum prevalence for molecularly confirmed and suspected disease was 2.9 (95% CI 2.4–3.4) and 1.8 (95% CI 1.4–2.2) cases per 100 000 respectively. Conclusions: Within the limitations of this study, comparison to similar prevalence studies performed by specialist referral centres suggests mitochondrial disease is underdiagnosed in NZ. This highlights a need for improved education and referral pathways for mitochondrial disease in NZ. [ABSTRACT FROM AUTHOR]

"Teaching and Learning About Family Literacy and Family Literacy Programs" is a comprehensive book that explores family literacy practices and programs in the USA, UK, and Canada. The authors emphasize the importance of family literacy programs in promoting literacy development in individuals, families, and communities. They discuss the different goals of adult education in relation to family literacy programs and highlight the benefits for both children and parents. The book also addresses the need for digital literacy integration and the importance of cultural sensitivity in family literacy programs. The authors recommend further research and documentation on various aspects of family literacy, including the role of fathers, incarcerated individuals, same-sex families, and developing nations. [Extracted from the article]

With advances in gene‐based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross‐sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age‐related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care. [ABSTRACT FROM AUTHOR]

India's expectation of a demographic dividend owing to an increase in the working age population necessitated government measures aimed at skilling youth. Considerable emphasis was therefore placed on skill development policies and programmes, including revamping formal vocational education and training (VET) institutions that provide skills to students completing secondary schooling and opting vocational training. Although the number of VET institutions in India more than doubled in the last decade, their underutilisation calls for an analysis of underlying reasons. This paper analyses socio-economic factors influencing participation in VET using data from nationally representative survey on education. Findings of a multinomial logit analysis in the paper suggest that students in upper secondary VET institutions tend to belong to socially disadvantaged households, and that students in vocational courses are more likely to be male, urban, and from households whose principal occupation is blue-collar. Children from households belonging to higher socio-economic status and pursuing white-collar jobs are more likely to participate in general and professional education as compared to VET because of higher status assigned to the former in the society. These findings call for fine-tuning of current polices of promotion of VET in India. [ABSTRACT FROM AUTHOR]

Objective: To assess diabetes eye service use in New Zealand among people aged ≥15 years by estimating service attendance, biennial screening rate, and disparities in the use of screening and treatment services. Methods: We obtained Ministry of Health data from the National Non-Admitted Patient Collection on diabetes eye service events between 1 July 2006 and 31 December 2019 and sociodemographic and mortality data from the Virtual Diabetes Register and linked these using a unique patient identifier (encrypted National Health Index). We 1) summarized attendance at retinal screening and ophthalmology services, 2) calculated biennial and triennial screening rate, 3) summarized treatment with laser and anti-VEGF and used log-binomial regression to examine associations of all of these with age group, ethnicity, and area-level deprivation. Results: In total, 245,844 people aged ≥15 years had at least one diabetes eye service appointment attended or scheduled; half of these (n = 125,821, 51.2%) attended only retinal screening, one-sixth attended only ophthalmology (n = 35,883, 14.6%) and one-third attended both (n = 78,300, 31.8%). The biennial retinal screening rate was 62.1%, with large regional variation (73.9% in Southern District to 29.2% in West Coast). Compared with NZ Europeans, Māori were approximately twice as likely to never receive diabetes eye care or to access ophthalmology when referred from retinal screening, 9% relatively less likely to receive biennial screening and received the fewest anti-VEGF injections when treatment was commenced. Disparities in service access were also present for Pacific Peoples compared to NZ Europeans, younger and older age groups compared to those aged 50–59 years and those living in areas with higher deprivation. Conclusions: Access to diabetes eye care is suboptimal, with substantial disparity between age groups, ethnicity groups, area level deprivation quintile and across districts. Efforts to improve access to and quality of diabetes eye care services must include strengthening data collection and monitoring. [ABSTRACT FROM AUTHOR]

Background: With the promise of gene replacement therapy, eligible males and females with X‐linked inherited retinal dystrophy (XL‐IRD) should be identified. Methods: Retrospective observational cohort study to establish the phenotypic and genotypic spectrum of XL‐IRD within New Zealand (NZ). Thirty‐two probands, including 9 females, with molecularly proven XL‐IRD due to RP2 or RPGR mutations, and 72 family members, of which 43 were affected, were identified from the NZ IRD Database. Comprehensive ophthalmic phenotyping, familial cosegregation, genotyping, and bioinformatics were undertaken. Main outcome measures were: RP2 and RPGR pathogenic variant spectrum, phenotype in males and females (symptoms, age of onset, visual acuity, refraction, electrophysiology, autofluorescence, retinal appearance), and genotype–phenotype correlation. Results: For 32 families, 26 unique pathogenic variants were identified; in RP2 (n = 6, 21.9% of all families), RPGR exons 1–14 (n = 10, 43.75%), and RPGR‐ORF15 (n = 10, 34.3%). Three RP2 and 8 RPGR exons 1–14 variants are novel, rare, and cosegregate. Thirty‐one percent of carrier females were significantly affected, with 18.5% of families initially classified as autosomal dominant. Of five Polynesian families, 80% had novel disease‐causing variants. One Māori family showed keratoconus segregating with an ORF15 variant. Conclusions: Significant disease was present in 31% of genetically proven female carriers, often leading to an erroneous presumption of the inheritance pattern. Pathogenic variants in 44% of the families were in exon 1–14 of RPGR, more frequent than usually described, which may inform the gene testing algorithm. Proving cosegregation in families for novel variants and identifying affected females and males translates to optimised clinical care and potential for gene therapy. [ABSTRACT FROM AUTHOR]

Purpose: Indian government initiated several skill development policies and different types of vocational education and training (VET). Yet the participation in skill education is low because of poor labour market outcomes. This paper aims to calculate returns to skill education to understand the type of training that will have better labour market outcomes. Design/methodology/approach: In this paper nationally representative data from the periodic labour force survey (PLFS), collected by the national sample survey office for 2017–2018, are used to estimate the returns to formal and non-formal VET obtained (after different levels of general education) with the help of Heckman's two-stage method. Findings: Nearly 8% of the working-age population has received some form of VET (mostly non-formal), generating poor returns. For the overall population, formal on-job training (OJT) and full-time VET influence wage positively and significantly. Full-time VET obtained after secondary and below levels of education generates positive returns, whereas part-time VET is profitable only to those without formal education. At the graduate level, technical education obtained along with VET is associated with better wages. Originality/value: In India where a considerable proportion of the workforce is employed in the informal sector, different types of skill training like full-time, part-time and OJT influence labour market outcomes. This finding has policy implication for countries with large informal sector and calls for further research in such countries. [ABSTRACT FROM AUTHOR]

The Automated Neuropsychological Assessment Metrics (ANAM) is one of the most widely used and validated neuropsychological instruments for assessing cognition. The ANAM Test System includes a reporting tool, the ANAM Validity Indicator Report that generates scores for the embedded effort measure, the ANAM Performance Validity Index (APVI). The current study seeks to develop a proxy for the APVI, using raw subtest summary test scores. This would be useful for situations where the APVI score is unavailable (e.g. validity report not generated at the time of the assessment) or when the item level data needed to generate this score are inaccessible. ANAM scores from a large data set of 1,000,000+ observations were used for this retrospective analysis. Results of linear regression analysis suggest that the APVI can be reasonably estimated from the raw subtest summary test scores that are presented on the ANAM Performance Report. Clinically, this means that an important step in the interpretation process, checking the validity of test data, can still be performed even when the APVI is not available. [ABSTRACT FROM AUTHOR]

Objective: The Automated Neuropsychological Assessment Metrics (ANAM) has long been used to assess cognition in military samples before deployment and following injury. The purpose of this study was to explore the effects of various demographic factors on the ANAM4 Military Expanded (ANAM4 ME) performance of Special Operations Forces (SOF) and to provide regression-based normative data for clinicians working with SOF personnel. Method: The sample was a large active duty military sample of SOF and support personnel (n = 24,072) who were tested under a new baseline policy. Results: Performance differences based on demographic variables were generally small. In general, increasing age was associated with significantly worse performance, except on mathematical processing. Higher education level was associated with better performance on most subtests, as expected, but was associated with worse performance on spatial processing. Conclusion: This paper provides regression formulas for calculating adjusted scores based on the most relevant demographic variables, as well as base rates of obtaining one or more clearly above or below average scores across the entire ANAM4 ME battery. [ABSTRACT FROM AUTHOR]

Harboyan syndrome is a rare autosomal recessive disorder characterised by congenital hereditary endothelial dystrophy (CHED), with a later onset of sensorineural hearing loss, due to pathogenic variants in the SLC4A11 gene. Congenital cytomegalovirus (CMV) may also manifest with sensorineural hearing loss and visual impairment. We present a case of a 4-year-old girl, diagnosed at birth with a congenital CMV infection, but careful phenotyping and genetic testing permitted a more likely diagnosis of Harboyan syndrome. [ABSTRACT FROM AUTHOR]

Blue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cluster on Xq28. Here, we investigated the prevalence and the landscape of submicroscopic structural variants (SVs) at single-base resolution in BCM patients. We found that about one-third (n = 73) of the 213 molecularly confirmed BCM families carry an SV, most commonly deletions restricted to the OPN1LW/OPN1MW gene cluster. The structure and precise breakpoints of the SVs were resolved in all but one of the 73 families. Twenty-two families--all from the United States--showed the same SV, and we confirmed a common ancestry of this mutation. In total, 42 distinct SVs were identified, including 40 previously unreported SVs, thereby quadrupling the number of precisely mapped SVs underlying BCM. Notably, there was no "region of overlap" among these SVs. However, 90% of SVs encompass the upstream locus control region, an essential enhancer element. Its minimal functional extent based on deletion mapping in patients was refined to 358 bp. Breakpoint analyses suggest diverse mechanisms underlying SV formation as well as in one case the gene conversion-based exchange of a 142-bp deletion between opsin genes. Using parsimonious assumptions, we reconstructed the composition and copy number of the OPN1LW/OPN1MW gene cluster prior to the mutation event and found evidence that large gene arrays may be predisposed to the occurrence of SVs at this locus. [ABSTRACT FROM AUTHOR]

North Carolina Macular Dystrophy (NCMD) and Best Vitelliform Macular Dystrophy (BVMD) are rare autosomal dominant macular dystrophies. Both BVMD and NCMD have markedly variable expressivity. In some individuals, it can be difficult to differentiate between the two disease entities. Clinical findings including fundus photography, fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) were evaluated in 5 individuals with NCMD and 3 with BMD. Electrooculography (EOG) was performed in 2 NCMD subjects. Molecular diagnosis was performed using Sanger DNA sequencing. IRB approval was obtained. Five NCMD subjects had clinical findings indistinguishable from three of our BVMD subjects. Molecular diagnosis was confirmed in all but one BVMD subject who had an abnormal EOG prior to discovery of the BEST1 gene. Two NCMD subjects had an abnormal EOG with a normal ERG, which has been considered a unique feature of BVMD. SD-OCT in one BVMD subject demonstrated a small lucency/excavation into the choroid similar to that in grade 3 lesions of NCMD. Two NCMD subjects had elevated sub-macular lesions giving a pseudo-vitelliform appearance on OCT similar to BVMD. Best Vitelliform Macular Dystrophy can be a phenocopy of NCMD. There is considerable clinical overlap between NCMD and BVMD, which can cause diagnostic inaccuracies. Our new findings demonstrate that like BVMD, NCMD can also have an abnormal EOG with a normal ERG. The overlapping phenotypes of BVMD with NCMD may provide insights into the mechanisms of the macular changes. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to describe the phenotype and molecular genetic causes of X‐linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families. Methods: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain. Results: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae). Conclusion: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants. [ABSTRACT FROM AUTHOR]

Wildfire is the main disturbance in most boreal forests. In the prolonged absence of wildfire, ecosystem retrogression occurs, which is characterized by reduced productivity, plant biomass and belowground process rates. Previous evidence suggests that phosphorus (P) decreases during retrogression, but the mechanisms involved remain poorly understood. Here we use 1-D 31P and 2-D, 1H-31P NMR to characterize changes in humus P composition across a 5000 year post-fire chronosequence in northern Sweden, to understand why P availability declines during long term fire absence. Against expectations, humus P composition varied only modestly with increasing time since fire. Using a method to back-calculate the in situ soil organic P speciation, we found that it was dominated by biologically active compounds such as RNA (41%), phospholipids (28%) and DNA (22%). The concentration of DNA and pyrophosphate was 19% and 29% lower, respectively, on infrequently burnt than recently burnt islands, and the concentration of DNA, phospholipids and nucleotides was positively correlated with net primary productivity (NPP). Given the lack of evidence for the accumulation of "recalcitrant" P or a geochemical P sink, reductions in P availability during retrogression may be associated with impaired P cycling through slower decomposition rates, and increasing humus depth separating surface humus from P-rich mineral soil. Our findings align with observed negative relationships between NPP and organic P concentration across other chronosequences. They also suggest that changing fire regimes in the boreal zone could indirectly affect the P cycle through changes in NPP and soil microflora rather than through changes in humus P composition. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and characteristics of peripheral pigmented retinal lesions and the associated clinical and genetic findings in patients with pathogenic variants in the ABCA4 gene. Methods: Records at a single tertiary hospital were retrospectively reviewed to identify the presence of peripheral pigmented retinal lesions on wide-field retinal imaging in patients with ABCA4-associated disease, compared with an RDS/PRPH2 cohort, and an age-matched control group. Data on patient demographics, genetic variants, severity of disease, and phenotype were collected and assessed. Results: Of 91 patients with at least one pathogenic variant in the ABCA4 gene and fundal changes consistent with ABCA4 retinal dystrophy, 15 (16.5%) had peripheral pigmented retinal lesions in 20 eyes, and were bilateral in 6 patients. These flat, subretinal lesions were located in the mid- or far periphery, not involving the macula, and had well-defined borders. Most affected eyes had a solitary lesion (n = 18) with lesions more commonly present in the temporal half of the retina. Twenty-one unique genetic variants in ABCA4 were associated with these lesions. In 26 subjects (52 eyes) with RDS/PRPH-2-associated IRD, and in 30 age-matched controls (60 eyes), only one control eye had a pigmented lesion consistent with congenital hypertrophy of the retinal pigment epithelium and there were no peripheral pigmented lesions. Conclusions: Almost one-fifth of patients with ABCA4-associated retinopathy have peripheral pigmented retinal lesions. The presence of these lesions is associated with more severe disease with an earlier onset than in patients without the lesions, and is an aid to diagnosis. [ABSTRACT FROM AUTHOR]

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan–Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2–12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680–1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets. [ABSTRACT FROM AUTHOR]

Megalocornea and anterior megalophthalmos (megalocornea spectrum) disorders are typically defined by corneal diameter > 12.5 mm in the absence of elevated intraocular pressure. Clinical features overlap with keratoglobus but are distinct from buphthalmos and severe (globus) keratoconus. Megalocornea spectrum disorders and keratoglobus are primarily congenital disorders, often with syndromic associations; both can present with large and thin corneas, creating difficulty in diagnosis, however, only keratoglobus is typically progressive. Molecular genetics provide significant insight into underlying aetiologies. Nonetheless, careful clinical assessment remains intrinsic to diagnosis. Surgical management can be challenging due to the enlarged ciliary ring and weakened zonules in megalocornea spectrum disorders and the extreme corneal thinning of keratoglobus. In this review, the established literature on measurement of corneal diameter, diagnosis of megalocornea, anterior megalophthalmos and keratoglobus, differentiation from severe keratoconus, recent molecular genetics research and key surgical modalities in the management of these rare disorders are outlined and discussed. [ABSTRACT FROM AUTHOR]

Background: Obtaining a definitive neurofibromatosis type-1 (NF1) diagnosis may take years. The natural history of choroidal neurofibromas in NF1 is unknown. This study evaluates a predominantly pediatric patient cohort for ocular features in NF1, including presence and progression of choroidal abnormalities, to determine their natural history, relationship to other NF1 features, and additive value in NF1 diagnosis. Methods: Retrospective analysis of 106 patients referred for Ophthalmic monitoring or diagnosis of NF1 between January 2012 and December 2018. Clinical records and Near-Infrared Reflectance (NIR) Optical Coherence Tomography imaging were analyzed for prevalence and progression of choroidal neurofibromas on NIR, and relation to other NF1 diagnostic criteria. Results: 54.7% of patients referred had a confirmed NF1 diagnosis, and 45.4% were NF1 suspects. First ophthalmic review resulted in an additional 6.6% patients meeting the diagnostic criteria, and 14.2% later developed sufficient features (total n = 80). Choroidal neurofibromas were present in 75.7% of patients that had NIR imaging and met diagnostic criteria, and detected in the absence of, or prior to Lisch nodules in 13.5%. Progression in the size and number of choroidal neurofibromas occurred in 26 eyes (32.5%) of 14 patients (35.0%), all under 16 years old. Patients without choroidal neurofibromas at first examination never developed them over the study period. Conclusion: Choroidal neurofibromas, detected by NIR imaging, are common in NF1, present early with frequent progression, and represent an additional tool to aid NF1 diagnosis in young children. [ABSTRACT FROM AUTHOR]

New technology has allowed for the transition of computerized neurocognitive assessments to increasingly user-friendly mobile platforms. While this increased portability facilitates neurocognitive assessment in a wider variety of settings, this transition necessitates further examination of the psychometric properties of tests that have been previously validated on alternate platforms. The present study evaluated the test-retest reliability and practice effects for a new version of the Automated Neuropsychological Assessment Metrics (ANAM), ANAM Mobile, designed to be administered on a tablet computer. A total of 108 undergraduate students completed ANAM Mobile and returned after one week for repeated testing. Observed test-retest reliabilities were consistent with previously established estimates across similar time intervals and ranged from .55 (Simple Response Time) to .87 (Matching to Sample). Modest practice effects were observed. Base rates of reliable decline were low and suggested that declines on two or more tests are uncommon among healthy college students. The present study demonstrates that ANAM Mobile subtests have good-to-excellent reliability across a 7-day retest interval with minimal practice effects. Future research should explore within-subject reliability across repeated ANAM administrations on a tablet device and further examine retest reliabilities over varying time courses and in more diverse samples. [ABSTRACT FROM AUTHOR]

Senior-Løken syndrome (SLS) is a rare autosomal recessive disease characterised by nephronophthisis and retinal degeneration, and belongs to a group of genetically heterogeneous disorders known as the ciliopathies. Case report of a patient with genetically proven SLS presenting with headaches and swollen optic nerve heads, review of medical notes and ophthalmic imaging, with retinal photography, fundus autofluorescence, and OCT retinal nerve fibre layer analysis. We present findings in a 15 year old girl with Senior-Løken syndrome associated with compound heterozygous mutations in the SDCCAG8 gene, who initially presented with a retinal dystrophy, and subsequent renal failure requiring renal transplantation and immunosuppression. Four and a half years later, she presented with headaches, reduced vision and clinical findings of papilloedema. Cerebrospinal fluid analysis revealed a high opening pressure of 37cmH20 and neuroimaging was otherwise unremarkable. Treatment with a reduced dose of oral acetazolamide resulted in symptomatic relief of headaches, and resolution of optic nerve swelling. The association of intracranial hypertension in a ciliopathy is a rare occurrence. The aetiology of intracranial hypertension in this case is likely multi-factorial, due to renal transplantation, post-renal transplant medications and/ or weight gain. With evidence of cilia involvement in the central nervous system, ciliary dysfunction may contribute to intracranial hypertension, and should be considered in these patients presenting with headaches. Diagnosis may be difficult with advanced retinal degeneration and baseline retinal nerve fibre layer thinning. Treatment requires careful monitoring of renal function. [ABSTRACT FROM AUTHOR]

Background. The aim of the study was to identify the molecular genetic cause of two different Mendelian traits with ocular involvement present in the members of a single consanguineous Czech Roma family. Methods. We have performed ocular examination and review of medical records in two individuals diagnosed with nanophthalmos (proband and her father) and one individual followed for bilateral congenital cataract and microcornea (uncle of the proband). DNA of subjects with nanophthalmos was analysed by exome sequencing. Sanger sequencing was applied for targeted screening of potentially pathogenic variants and to follow segregation of identified variants within the family. Results. A homozygous variant c.1509G>C; p.(Met503Ile), in PRSS56 was found in the two individuals affected with nanophthalmos. The change was absent from the gnomAD dataset, but two out of 118 control Roma individuals were also shown to be heterozygous carriers. Analysis of single nucleotide polymorphisms in linkage disequilibrium with the c.1509G>C in PRSS56 suggested a shared chromosomal segment. The nanophthalmos phenotype, characterized in detail in the younger individual, encompassed bilateral corneal steepening, retinal folds, buried optic head drusen, and restricted visual fields, but no signs of retinal dystrophy. A known pathogenic founder CTDP1 variant c.863+389C>T in a homozygous state was identified in the other family member confirming the suspected diagnosis of congenital cataracts, facial dysmorphism, and demyelinating neuropathy syndrome. Conclusions. Herein, we report the first occurrence of nanophthalmos in the Roma population. We have identified pseudodominant inheritance for this phenotype caused by a novel variant in PRSS56, representing a possible founder effect. Despite advances in genetic technologies such as exome sequencing, careful phenotype evaluation in patients from an isolated population, along with an awareness of population-specific founder effects, is necessary to ensure that accurate molecular diagnoses are made. [ABSTRACT FROM AUTHOR]

Tropical rainforests harbor exceptionally high biodiversity and store large amounts of carbon in vegetation biomass. However, regional variation in plant species richness and vegetation carbon stock can be substantial, and may be related to the heterogeneity of topoedaphic properties. Therefore, aboveground vegetation carbon storage typically differs between geographic forest regions in association with the locally dominant plant functional group. A better understanding of the underlying factors controlling tropical forest diversity and vegetation carbon storage could be critical for predicting tropical carbon sink strength in response to projected climate change. Based on regionally replicated 1-ha forest inventory plots established in a region of high geomorphological heterogeneity we investigated how climatic and edaphic factors affect tropical forest diversity and vegetation carbon storage. Plant species richness (of all living stems >10 cm in diameter) ranged from 69 to 127 ha−1 and vegetation carbon storage ranged from 114 to 200 t ha−1. While plant species richness was controlled by climate and soil water availability, vegetation carbon storage was strongly related to wood density and soil phosphorus availability. Results suggest that local heterogeneity in resource availability and plant functional composition should be considered to improve projections of tropical forest ecosystem functioning under future scenarios. [ABSTRACT FROM AUTHOR]

Coated-platelets are a subset of highly procoagulant platelets elevated in patients with non-lacunar ischemic stroke and associated with stroke recurrence. Cross-sectional studies in controls have shown that smoking is associated with higher coated-platelet levels while chronic use of serotonin reuptake inhibitors (SSRIs), statins or aspirin is associated with lower coated-platelet levels. We now investigate if initiation of treatment with SSRIs, statins, clopidogrel, aspirin or oral anticoagulants and smoking cessation impacts coated-platelet levels at 90 days after ischemic stroke. Coated-platelet levels, reported as percent of cells converted to coated-platelets, were measured in 87 consecutive patients with stroke at baseline and repeated at 90 days. Repeated-measure ANOVA was used to determine if initiation of treatment with individual medications or smoking cessation impacted coated-platelet levels. Decreased coated-platelets levels at 90 days as compared to baseline were observed after initiation of treatment with clopidogrel (p =.0001, partial η2 = 0.17) and smoking cessation (p =.014, partial η2 = 0.10). Initiation of treatment with SSRIs, statins, aspirin or oral anticoagulants did not result in significant changes in coated-platelet potential. These novel longitudinal data suggest that clopidogrel therapy and smoking cessation attenuate coated-platelet potential at 90 days after ischemic stroke. [ABSTRACT FROM AUTHOR]

To examine differences in incidence, prevalence and screening for diabetic retinopathy in New Zealand, we searched MEDLINE, EMBASE and CINAHL up to 6 December 2018 for observational studies reporting diabetic eye disease or attendance at retinal screening, disaggregated by ethnicity. Two authors separately screened and selected studies, and extracted data. None of the 11 included studies reported data on visual impairment from diabetic retinopathy. All nine studies reporting diabetic eye disease by ethnicity found Pacific people and Māori had higher rates of sight‐threatening disease and lower rates of screening attendance compared to Europeans. Data for Asian people were infrequently reported, but when they were, they also fared worse than Europeans. This review highlights that equity‐focused strategies are needed to address ethnic disparities in eye health among New Zealanders with diabetes. The review also identifies how research methods can be strengthened to enable future calculation of robust disease prevalence estimates. [ABSTRACT FROM AUTHOR]

Women have smaller cortisol responses to psychological stress than men do, and women taking hormonal contraceptives (HC+) have smaller responses than HC− women. Cortisol secretion undergoes substantial diurnal variation, with elevated levels in the morning and lower levels in the afternoon, and these variations are accompanied by differences in response to acute stress. However, the impact of HC use on these diurnal relationships has not been examined. We tested saliva cortisol values in 744 healthy young adults, 351 men and 393 women, 254 HC− and 139 HC+, who were assigned to morning (9:00 am) or afternoon (1:00 pm) test sessions that were held both on a rest day and on a stress day that included public speaking and mental arithmetic challenges. Saliva cortisol responses to stress were largest in men and progressively smaller in HC− and in HC+ women (F = 23.26, p <.0001). In the morning test sessions, HC+ women had significantly elevated rest day cortisol levels (t = 5.99, p ≪.0001, Cohen's d = 0.95) along with a complete absence of response on the stress day. In the afternoon sessions, both HC+ and HC− women had normal rest-day cortisol levels and normal responses to the stressors. Heart rates at rest and during stress did not vary by time of day or HC status. Cortisol stress responses in HC+ women are absent in the morning and normal in size by early afternoon. Studies of stress reactivity should account for time of day in evaluating cortisol responses in women using hormonal contraceptives. [ABSTRACT FROM AUTHOR]

Background: Risk for alcoholism may be enhanced by exposure to early‐life adversity (ELA) in persons with genetic vulnerabilities. We examined ELA in the presence of a common variant of the gene for the enzyme catechol‐O‐methyltransferase (COMT, Val158Met, rs4680) in relation to cortisol reactivity, the onset of early drinking, and experimentation with drugs. Methods: Saliva cortisol reactivity to speech and mental arithmetic stress was measured in 480 healthy young adults (23.5 years of age, 50% females) who experienced either 0, 1, or ≥ 2 forms of ELA during childhood and adolescence, provided information on use of alcohol and recreational drugs, and were genotyped for the Val158Met polymorphism. Results: ELA led to progressively smaller cortisol responses in the Met/Met and Val/Met allele groups but to progressively larger responses in Val homozygotes, F = 3.29, p = 0.011. ELA independently predicted earlier age at first drink, F = 14.2, p < 0.0001, with a larger effect in Met‐allele carriers, F = 13.95, p < 0.00001, and a smaller effect in Val homozygotes, F = 4.14, p = 0.02. Similar effects were seen in recreational drug use. Cortisol reactivity was unrelated to drinking behavior or drug experimentation. Conclusions: ELA leads to blunted stress reactivity and, independently, contributes to potentially risky drinking and drug‐use behaviors in persons carrying 1 or 2 copies of the COMT 158Met allele. The results reinforce the impact of early experience on the stress axis and on risky behaviors, and they point to the 158Met allele as conveying a vulnerability to the early environment. [ABSTRACT FROM AUTHOR]

Early life adversity (ELA) negatively affects health behaviors in adulthood, but pathways from ELA exposure to behavioral outcomes are poorly understood. ELA in childhood and adolescence may translate into adult outcomes by way of modified glucocorticoid signaling. The cortisol cotransporter, FKBP5 has a G-to-A substitution (rs9296158) that hinders cortisol trafficking within target cells, and this impaired glucocorticoid signaling may shape the long-term response to ELA. We used performance on the Stroop test to assess working memory in 546 healthy young adults who had experienced 0, 1, or > 1 forms of ELA in childhood and adolescence and were genotyped for the FKBP5 rs9296158 G-to-A polymorphism. We observed a robust Gene x Environment interaction (F = 9.49, p < .0001) in which increased ELA exposure led to progressively greater Stroop interference in persons carrying AG and AA genotypes of FKBP5 with no such effect in GG carriers. Further work is needed to explore the modification of cognitive function resulting from ELA. Impairments in working memory illustrate how ELA may use glucocorticoid pathways to influence working memory with potential implications for decision-making and risky behavior including substance use disorders. [ABSTRACT FROM AUTHOR]

Background and aims: People with blunted stress reactivity have poor impulse control and also show increased risk for alcoholism. Exposure to early life adversity (ELA) contributes to blunted reactivity, but individual differences in susceptibility to ELA are not well understood. This study aimed to determine whether exposure to ELA has a greater impact on stress reactivity in young adults with a family history of alcoholism (FH+) compared with young adults with no family history of alcoholism (FH–). Design Observational study using linear modeling. Setting: Oklahoma, USA. Participants: Seven hundred and nine young adults (398 females) recruited through community advertisement. Measurements We obtained heart rates and cortisol levels in subjects while undergoing public speaking and mental arithmetic stress compared with a resting control day (1418 test sessions). ELA was quantified as 0, 1 or > 1 adverse events experienced by age 15 years. FH+ people had one or two parents with an alcohol use disorder, and FH– controls had no such history for two generations. Findings Increasing levels of ELA predicted progressive blunting of cortisol and heart rate reactivity for the whole sample (Fs = 4.57 and 4.70, Ps ≤ 0.011), but examination by FH status showed that the effect of ELA was significant only among FH+ (Fs ≥ 3.5, Ps < 0.05) and absent in FH– (Ps > 0.40). This difference in ELA impact was not explained by the cortisol diurnal cycle or subjective evaluation of the stressors. Conclusions: People with a family history of alcoholism appear to be vulnerable, in terms of changes to physiological stress response, to the impact of exposure to early life adversity while people with no family history of alcoholism appear to be resilient. Blunted stress reactivity may reflect differential vulnerability to early life adversity in young adults with a family history of alcoholism. [ABSTRACT FROM AUTHOR]

Aōtearoa/New Zealand is a small island nation at the bottom of the South Pacific, with a population of 5 million, and the largest Polynesian population in the world. 15% identify as Māori, and 7% as Pacific Peoples, and the spectrum of inherited eye disease encountered in this population varies from that seen in those identifying as NZ European. Keratoconus is more common, while primary open angle glaucoma is rare. A founder PDE6B variant has been identified causing up to 16% of autosomal recessive inherited retinal disease (IRD) in the Māori population. This genetically homogenous cohort permits a clear natural history for PDE6B IRD. Recurrent pathogenic variants, some novel, are also found in other IRD genes including SNRNP200 and PRPH2. Although many of those with inherited retinal disease remain genetically uncharacterised, research to date shows a range of novel variants in a many genes, but also allows exclusion of other variants of uncertain significance, due to their frequency in this cohort. There is a need for genetics researchers to have a cultural awareness of the population, and acknowledge the socioeconomic and health disparities which result in late presentation. Documentation of the specific genetic disease spectrum, clinical phenotypes, and a knowledge of regional ancestry and iwi (tribe), aids in simplifying the diagnostic process. [ABSTRACT FROM AUTHOR]

Early life adversity (ELA) contributes to behavioral impulsivity along with risk for substance use disorders, both accompanied by blunted stress-axis reactivity. However, the biological contributors to blunted stress reactivity are not known. We took advantage of the fact that women have significant opioid inhibition of cortisol output by using the opioid antagonist, naltrexone, to unmask opioid interactions due to ELA. We administered 50 mg of naltrexone or placebo to 72 healthy women (23 years of age) in a double-blind crossover study and observed deviations in cortisol secretion from placebo over the next 180 minutes. ELA was assessed by reported exposure to physical and sexual abuse or neglect and low socioeconomic status and scored as Low, Medium, or High (0, 1–2, and 3+). The ELA groups all had identical placebo-day cortisol secretion, indicating normal basal regulation of the hypothalamic-pituitary-adrenocortical axis. Cortisol rises to naltrexone were largest in the Low-ELA group and strongly blunted in the High-ELA group (F = 3.51, p = 0.035), indicating a lack of opioid function in women with high degrees of ELA. The Low-ELA women reported dysphoric responses to naltrexone (F = 4.05, p = .022) indicating a mild opioid withdrawal, an effect that was absent in the High-ELA group. Women exposed to ELA have blunted cortisol responses to naltrexone, indicating reduced opioid regulation of the stress axis. Central opioid changes may be one pathway linking ELA to blunted stress reactivity in adulthood. [ABSTRACT FROM AUTHOR]

The Automated Neuropsychological Assessment Metrics (ANAM) is a library of computer based tests designed to measure cognitive function at a single time-point or longitudinally for detection of cognitive change. This study sought to validate ANAM as a cognitive screening tool for presence of confirmed neuropsychological diagnosis in an outpatient setting. Retrospective data analysis was conducted for 139 patients referred for outpatient neuropsychological assessment. Clinical diagnosis was made independent of ANAM test results and resulted in a diagnostic mix of both neurologic and psychologic etiologies. ANAM scores predictive of presence of confirmed diagnosis were identified using multiple logistic regression and the predictive ability of the resulting model was quantified using receiver operator characteristic analysis. Sensitivity and specificity for the ANAM when combined with anger and depressive symptom scores were 71% and 91%, respectively, with a positive predictive value of 97.5 and negative predictive value of 40.4. This combined approach provided the greatest accuracy for individual tests as well as the composite score of the ANAM in identifying those who received a subsequent clinical diagnosis. Although data should be replicated in larger samples, these results suggest that ANAM may have predictive value and may be a useful screening tool for identifying those who would likely benefit from neuropsychological services. [ABSTRACT FROM AUTHOR]

Objective: As the use of computer-based neurocognitive assessment is rapidly expanding, the need to systematically study and document key psychometric properties of these measures has become increasingly more salient. To meet this aim, this study examined test-retest reliability and practice effects for the Automated Neuropsychological Assessment Metrics General Neuropsychological Screening battery (ANAM GNS) in a sample of 94 community dwelling adults. Method: ANAM GNS was administered and then repeated (alternate form) after 30 days. Test-retest reliability, practice effects, and the standard error of measurement were calculated. Using these estimates, reliable change indices were calculated to determine degree of performance change needed to exceed chance and measurement error (with 90% confidence interval). Results: The test-retest reliability for the ANAM composite score was .91. Performance significantly improved upon retest, but the effect size was small consistent with minimal practice effects. The threshold indicating change beyond chance or measurement error with 90% certainty was .9 (z-score). Conclusions: Findings suggest that the ANAM GNS has excellent test-retest reliability upon retest at 30 days. Small practice effects can be expected. Change greater than .9 standard deviations in the ANAM composite score is likely to represent meaningful clinical change. This paper presents initial psychometric data from the ANAM GNS and supports its use as a reliable measure of cognition. [ABSTRACT FROM AUTHOR]

A bilaterally blind woman, with a three generation family history of autosomal dominant congenital cataracts, variably associated with iris colobomata and microcornea, sought preconception genetic consultation. Whole-exome sequencing was performed in three affected family members, one unaffected first degree relative, and one spouse. The sequence variant c.168C>G; p.(Tyr56∗) in CRYGD, previously reported as pathogenic, and a novel mutation c.809C>A; p.(Ser270Tyr) in MAF, were identified in two affected family members; the grandmother, and half-brother of the proband. The proband inherited only the MAF mutation, whereas her clinically unaffected sister had the CRYGD change. In silico analysis supported a pathogenic role of p.(Ser270Tyr) in MAF, which was absent from publicly available whole-exome datasets, and 1161 Czech individuals. The frequency of CRYGD p.(Tyr56∗) in the ExAC dataset was higher than the estimated incidence of congenital cataract in the general population. Our study highlights that patients with genetically heterogeneous conditions may exhibit rare variants in more than one disease-associated gene, warranting caution with data interpretation, and supporting parallel screening of all genes known to harbour pathogenic mutations for a given phenotype. The pathogenicity of sequence variants previously reported as cataract-causing may require re-assessment in light of recently released datasets of human genomic variation. [ABSTRACT FROM AUTHOR]

Background: To clinically characterize a cohort of patients with ectopia lentis (EL), or Marfanoid features in whom a definite genetic diagnosis of Marfan syndrome (MFS) had been excluded (atypical MFS), and to evaluate the contribution of mutations inADAMTSL4(OMIM 610113), andP3H2 (LEPREL1; OMIM 610341) to disease in this population. Materials and Methods: Subjects underwent comprehensive ophthalmic examination, including keratometry. Mutational analysis ofADAMTSL4andP3H2was undertaken using PCR, high resolution melting analysis, and sequencing. The frequency of c.2237G>A; p.(Arg746His) was determined in an unaffected Polynesian cohort. Haplotype analysis used tagged single nucleotide polymorphic markers. Results: Mutational analysis ofADAMTSL4identified two pathogenic variants inADAMTSL4in 11/31 (35%) probands, consistent with the autosomal recessive EL phenotype. A recurrent, rare missense variant inADAMTSL4, c.2237G>A; p.(Arg746His), was present in 10 probands –(8 homozygotes), predominantly of Polynesian descent, and all shared the same haplotype. p.(Arg746His) affects the Thrombospondin1 (TSP1) domain of the protein and is predicted to be pathogenic. No pathogenic variants inP3H2were identified. Conclusion: A recurrent pathogenicADAMTSL4variant is a major cause of early onset autosomal recessive EL in a Cook Island Māori population and associated with a common haplotype, suggesting a founder effect. Children presenting under the age of 5 years, particularly of Cook Island or New Zealand Māori descent, with isolated ectopia lentis, should in the first instance be tested for this single variant. [ABSTRACT FROM AUTHOR]

Importance: This study identifiesunique genetic variation observed in a cohort of Māori and Polynesian patients with rod-cone retinal dystrophies using a targeted nextgeneration sequencing retinal disease gene panel. Background: With over 250 retinal disease genes identified, genetic diagnosis is still only possible in 60-70% of individuals and even less within unique ethnic groups. Design: Prospective genetic testing in patients with rod-cone retinal dystrophies identified from the New Zealand Inherited Retinal Disease Database, Participants: Sixteen patients of Māori and Polynesian ancestry. Methods: Next-generation sequencing of a targeted retinal gene panel. Sanger sequencing for a novel PDE6B mutation in subsequent Māori patients. Main Outcome Measures: Genetic diagnosis, genotype-phenotype correlation. Results: Thirteen unique pathogenic variants were identified in 9 of 16 (56.25%) patients in 10 different genes. A definitive genetic diagnosis was made in 7/16 patients (43.7%). Six changes were novel and not in public databases of human variation. In four patients, a homozygous, novel pathogenic variant (c.2197G > C, p.(Ala 733Pro)) in PDE6B was identified and also present in a further five similarly affected Māori patients. Conclusions and Relevance: Over half of the Māori and Polynesian patients with inherited rod-cone diseases have no pathogenic variant(s) detected with a targeted retinal next-generation sequencing strategy, which is supportive of novel genetic mechanisms in this population. A novel PDE6B founder variant is likely to account for 16% of recessive inherited retinal dystrophy inMāori. Careful characterization of the clinical presentation permits identification of further Māori patients with a similar phenotype and simplifies the diagnostic algorithm. [ABSTRACT FROM AUTHOR]

The BrainScope Ahead 300 is designed for use by health care professionals to aid in the assessment of patients suspected of a mild traumatic brain injury. The purpose of the current study was to establish normative data for the cognitive test component of the Ahead 300 system and to evaluate the role of demographic factors on test performance. Healthy, community-dwelling adults between the ages of 18 and 80 recruited from five geographically distributed sites were administered Android versions of the ANAM Matching to Sample and Procedural Reaction Time tests that comprise the cognitive test component of the Ahead 300 system by trained personnel. Scores were correlated with age, education, and race. Age accounted for the majority of the variance in test scores with additional significant, but minor, contributions of education and race. Gender did not account for a significant proportion of the variance for either test. Based on these results, the normative data for 551 individuals are presented stratified by age. These are the first available normative data for these tests when administered using the Ahead 300 system and will assist health care professionals in determining the degree to which scores on the cognitive tests reflect impaired performance. [ABSTRACT FROM AUTHOR]

The article presents a case study of an Asian patient diagnosed with Bietti Crystalline Dystrophy (BCD) which is an autosomal recessive progressive condition. It mentions that Optical Coherence Tomography (OCT) confirms the existence of multiple intraretinal hyperreflective lesions in neurosensory retina. It reports the visual symptoms including central vision loss and nyctalopia.

A 2-year-old presented with lethargy, acute visual loss, fixed dilated pupils and severe bilateral retinal haemorrhages. The retinal findings raised concerns about abusive head trauma, but subsequent investigations confirmed the diagnosis of bilateral optic neuritis associated with acute disseminated encephalomyelitis. [ABSTRACT FROM AUTHOR]

A 2-year-old presented with lethargy, acute visual loss, fixed dilated pupils and severe bilateral retinal haemorrhages. The retinal findings raised concerns about abusive head trauma, but subsequent investigations confirmed the diagnosis of bilateral optic neuritis associated with acute disseminated encephalomyelitis. [ABSTRACT FROM AUTHOR]

Background Mutations in FOXL2 are known to cause autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure. In this study, we report results of mutational screening in a Czech and Slovak patient population with BPES. Design Case series. Participants Thirteen probands of Czech and one proband of Slovak origin with BPES and their available family members. Methods Sanger sequencing and multiplex ligation-dependent probe amplification in 14 probands with BPES. Targeted mutational screening in first-degree relatives. Main Outcome Measures Genetic characterization and phenotype evaluation in Czech and Slovak individuals with BPES and their family members. Results Eight different mutations were detected including three novel ones: c.5T>G; p.(Met2Arg), c.197C>A; p.(Ala66Glu) and c.701_702insTGCAGCCGCAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC; p.(Ala222_Ala234dup). In one family, the molecular genetic cause of disease was not identified by the methodology used. In 13 pedigrees, a negative family history suggested a de novo origin, which could be confirmed by targeted mutational screening in four families. One 62-year-old female with the c.663_692dup30 mutation had an atypical phenotype presenting as moderate ptosis compensated by frontalis muscle contraction, no epicanthus inversus and no premature ovarian failure. Conclusions The de novo mutation rate in FOXL2 is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. In cases reporting a negative family history, careful examination of both parents is important to exclude mild features of the BPES phenotype. [ABSTRACT FROM AUTHOR]

We observed bilateral cataracts on second trimester ultrasound, in two consecutive pregnancies, with no other structural defects detected. The parents were unrelated and had no family history for the disease. The first pregnancy was terminated in week 22. Copy number variation analysis revealed, in both the aborted fetus and the mother, a 495 kb duplication at 22q11.23 encompassing CRYBB3 and CRYBB2, and not present in variation databases. In the second pregnancy, lens hyperechogenicity was detected by ultrasound at week 13 and 4 days. The identical duplication at 22q11.23 was found in the fetus and considered as possibly pathogenic. At weeks 22 and 30, smaller orbit measurements were elucidated on ultrasound, raising concerns as to the underlying molecular genetic cause, necessitating further investigation. Whole-exome sequencing, using DNA of the first fetus, was performed shortly after the birth of a male child, and two truncating RAB3GAP1 mutations were detected: c.538G>T; p. (Glu180*) and c.943C>T; p. (Arg315*). Neither mutation has been previously reported to be disease-causing; however, evaluation in the context of previously published literature indicated their deleterious nature, implying a clinical diagnosis of Warburg micro syndrome or Martsolf syndrome. Sanger sequencing confirmed segregation of the two mutations within the family, consistent with autosomal recessive inheritance. The child born from the second pregnancy showed features typical of Warburg micro syndrome, with the exception of microcephaly, at age 31 months. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]