An unusual presentation of extra-hepatic portal venous obstruction

A 13-year-old girl presented with short duration of fever, left upper abdominal pain and massive tender splenomegaly. There was noevidence of liver dysfunction or significant history. Evaluation revealed multiple splenic infarcts with portal vein thrombosis. Shedeveloped splenic abscess and was managed conservatively with percutaneous drainage and antibiotics

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Spectacle compliance among adolescents in Southern India: Perspectives of service providers

Purpose: Compliance to spectacle wear is vital to elimination of avoidable blindness among schoolchildren. This study aims to understand the barriers to compliance and strategies to overcome the barriers from the perspectives of the service providers of the school vision-screening model. Methods: A snapshot qualitative study using focus group discussions (FGDs) was conducted among the service providers including eye care professionals (ECPs) and social workers that are part of the school screening program. Sessions were audio recorded and transcribed. Themes were formed following inductive coding using a conceptual framework. Results: Out of the three FGDs, two were with ECPs and one with social workers. Four subthemes identified under the barriers were poor awareness, spectacle-related, psychosocial, and financial barriers. Unique barriers according to the service providers included nonuse of spectacles by asymptomatic children, children with unilateral refractive errors and those with emmetropic parents. Service providers also brought out parent's feelings of guilt, doubts about their children's impaired vision, the negative self-image among children, and difficulties in obtaining funding to support the costs of screening. Solutions that emerged included the personal visit of professionals for spectacle distribution and counseling parents, demonstration of improvement in vision for activities that were difficult for the children without spectacles and rewarding, and role modeling of compliant children. Conclusion: This study had identified unique barriers and solutions from the perspectives of the service providers. The suggested strategies would aid in an effective schoolchildren vision screening practice to enhance compliance to spectacle wear

Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients

Genetic studies in a patient with X-linked retinoschisis coexisting with developmental delay and sensorineural hearing loss

<p><i>Background</i>: In this study, we present a juvenile retinoschisis patient with developmental delay, sensorineural hearing loss, and reduced axial tone. X-linked juvenile retinoschisis (XLRS) is a retinal dystrophy, most often not associated with systemic anomalies and also not showing any locus heterogeneity. Therefore it was of interest to understand the genetic basis of the condition in this patient.</p> <p><i>Materials and methods: RS1</i> gene screening for XLRS was performed by Sanger sequencing. Whole genome SNP 6.0 array analysis was carried out to investigate gross chromosomal aberrations that could result in systemic phenotype. In addition, targeted next generation sequencing (NGS) was employed to determine any possible involvement of X-linked syndromic and non-syndromic mental retardation genes. This NGS panel consisted of 550 genes implicated in several other rare inherited diseases.</p> <p><i>Results: RS1</i> gene screening revealed a pathogenic hemizygous splice site mutation (c.78+1G>T), inherited from the mother. SNP 6.0 array analysis did not indicate any significant chromosomal aberrations that could be disease-associated. Targeted resequencing did not identify any mutations in the X-linked mental retardation genes. However, variations in three other genes (<i>NSD1, LARGE</i>, and <i>POLG</i>) were detected, which were all inherited from the patient’s unaffected father.</p> <p><i>Conclusions</i>: Taken together, <i>RS1</i> mutation was found to segregate with retinoschisis phenotype while none of the other identified variations were co-segregating with the systemic defects. Hereby, we infer that the multisystemic defects harbored by the patient are a rare coexistence of XLRS, developmental delay, sensorineural hearing loss, and reduced axial tone reported for the first time in the literature.</p