Curvularia lung infection mimics malignancy

Curvularia rarely causes human infections despite its ubiquity in the environment. It is most associated with allergic diseases such as chronic sinusitis and allergic bronchopulmonary mycosis; however, causing a lung mass is rarely reported in the literature. We describe an interesting case of a 57-year-old man with a history of asthma and localized prostate cancer diagnosed with a Curvularia-caused lung mass that responded quickly to itraconazole

The spectrum of leukodystrophies in children: Experience at a tertiary care centre from North India

Objective: The objective of this study is to retrospectively collect and then describe the clinico-radiographical profile of confirmed cases of leukodystrophy who presented over a 5-year period to a tertiary care teaching hospital in North India. Materials and Methods: The case records of 80 confirmed cases of leukodystrophy were reviewed and the cases have been described in terms of their clinical presentation and neuroimaging findings. Results: The cases have been grouped into five categories: Hypomyelinating, demyelinating, disorders with vacuolization, cystic, and miscellaneous. The commonest leukodystrophies are megalencephalic leukoencephalopathy with subcortical cysts (MLC), Pelizaeus-Merzbacher disease (PMD), and metachromatic leukodystrophy (MLD). A notable proportion of hypomyelinating disorders were uncharacterized. Conclusions: Leukodystrophies at this point of time have no definite cure. They have a progressively downhill clinical course. Early diagnosis is imperative for appropriate genetic counseling. A simplified approach to diagnose common leukodystrophies has also been provided. It is important to develop a registry, which can provide valuable epidemiological data to prioritize research in this field, which has many unanswered questions

Epigenetic regulation of cytomegalovirus major immediate-early promoter activity in transgenic mice

The expression of genes in transgenic mice is known to be influenced by the site of integration even when they carry their own promoter elements and transcription factor binding sites. The cytomegalovirus (CMV) promoter, a strong promoter often used for transgene expression in mammalian cells in culture, is known to be silenced by DNA methylation and histone deacetylation but there is no report on the role of histone methylations in its regulation. We generated two transgenic lines carrying green florescence protein coding gene as reporter driven by cytomegalovirus major immediate-early promoter/enhancer. We observe that silencing of CMV promoter is dependent on the site of transgene integration, except in testis, and the nature of DNA and histone methylations strongly correlate with the expression status of the reporter. We find that silenced CMV promoter interacts in vivo, with Methyl CpG binding protein 2 (MeCP2), a recruiter of histone deacetylases (HDACs) and histone (H3K9) methyl transferase. Histone H3K4methylation, the active chromatin mark, is also associated with silenced promoter, suggesting bivalent marking of the promoter and its susceptibility to reactivation on induction

Mutations in OCRL1 gene in Indian children with Lowe syndrome.

International audienceBACKGROUND: Lowe syndrome is an X-linked disorder secondary to mutations involving the OCRL1 gene. There are no data on the spectrum of the disease in the Asian population. METHODS: Detailed clinical assessment, a laboratory assessment which included both glomerular and tubular function tests and genomic DNA analysis, was carried out in six unrelated patients with Lowe syndrome. RESULTS: Analysis of this gene in six unrelated patients with Lowe syndrome showed novel mutations in four and previously described mutations in two. These included a missense mutation (exon 10), two nonsense mutations (exons 10 and 21), two frameshift mutations (exons 12 and 21) and a mutation at the acceptor site of intron 22. The mothers were found to be heterozygote carriers in four cases. CONCLUSIONS: This is the first report of mutations involving the OCRL1 gene in patients with Lowe syndrome of Indian origin. These observations have implications for genetic counseling and prenatal diagnosis for families with Lowe syndrome

Comparative analysis of DNA methylation in transgenic mice with unstable CGG repeats from FMR1 gene

Methylation of CpG sequences in and around CGG triplet repeats in FMR1 gene has strong correlation with manifestation of the fragile X syndrome in human patients. In contrast, we have observed a lack of correlation between repeat instability and DNA methylation in three different transgenic mouse models harboring unstable CGG repeats. Further we have demonstrated that the endogenous copy of mouse Fmr1 gene remains unmethylated both in males and females. These results imply that methylation and repeat instability are independent events and raise the possibility that methylation could also result in repression of FMR1 transcription in the absence of repeat expansion

Abnormal V(D)J recombination of T cell receptor β locus in SMAR1 transgenic mice

Scaffold/matrix-associated region-1-binding protein (SMAR1) specifically interacts with the MARβ sequence, which is located 400-bp upstream of the murine TCRβ enhancer and is highly expressed during the DP stage of thymocyte development. To further analyze the functions of SMAR1, transgenic mice were generated that express SMAR1 in a tissue-independent manner. SMAR1-overexpressing mice exhibit severely altered frequency of the T cells expressing commonly used Vβs (Vβ5.1/5.2 and Vβ8.1/8.2/8.3). The rearrangements of Vβ5.1/5.2, Vβ8.1/8.2/8.3 loci are also reduced in SMAR1 transgenic mice. The T cells in SMAR1 transgenic mice exhibit a mild perturbation at the early DN stage. SMAR1 transgenic mice exhibit hypercellular lymph nodes and spleen accompanied with prominent architectural defects in these organs. These results indicate that SMAR1 plays an important role in the regulation of T cell development as well as V(D)J recombination besides maintaining the architecture of the lymphoid organs

Instability of CGG Repeats in Transgenic Mice

Dynamic mutation resulting in the expansion of CGG repeats in the untranslated region (UTR) of the first exon of the FMR1 gene in humans results in fragile X syndrome. Long stretches of CGG repeats that are known to be highly unstable in humans have so far failed to show similar intergenerational instability in transgenic mice. We generated transgenic lines that show a dramatic increase from 26 to >300 repeats in three generations. One of the salient features of our transgene is the inclusion of the origin of replication of simian virus-40 (SV40), which is known to exclude nucleosomes. Three founder mice in FVB/NJ background show expansion of CGG repeats present in the transgene, supporting a postzygotic mechanism for CGG expansion that is independent of a genomic imprinting effect. We discuss here the results of analyzing one of the lines established

A novel homozygous mutation in POLR3A gene causing 4H syndrome: a case report

Abstract Background 4H syndrome is a congenital hypomyelinating leukodystrophy characterized by hypodontia, hypomyelination and hypogonadotropic hypogonadism belonging to the Pol III-related leukodystrophies which arise due to mutations in the POLR3A or POLR3B gene. The clinical presentation is of neurodevelopmental delay or regression with ataxia, dystonia, nystagmus, delayed deciduous dentition and abnormal order of eruption of teeth. MRI brain shows a characteristic hypomyelination pattern. Several mutations have been described in the implicated genes but there are no reports on mutations seen in patients from India. Case presentation We report a 1½ year old girl, only child of a non-consanguinous couple who presented with delayed developmental milestones and delayed dentition. On physical examination she had downward slanting palpebral fissures, low set ears, smooth philtrum, hypodontia, prominent body hair and clitoromegaly. There was prominent horizontal nystagmus, hypertonia of both upper and lower limbs, exaggerated deep tendon jerks and flexor planter response. She had not attained complete head control and required support to sit. She showed absent waves on brainstem evoked response audiometry and her fundus examination showed bilateral optic atrophy with prolongation of P100 latencies on visual evoked potentials. MRI Brain showed hyperintensity of entire white matter with involvement of the internal and external capsule, frontal deep white matter and corpus callosum. Her karyotype was 46 XX and her endocrinal profile was unremarkable. Clinical exome sequencing identified an unreported mutation in the POLR3A gene. The same mutation was identified by Sanger sequencing in heterozygous state in both parents. The child is being managed with physiotherapy and developmental therapy. She has been provided with hearing aids and started on speech therapy. Parents were provided anticipatory guidance and genetic counselling about autosomal recessive nature of inheritance, risk of recurrence and need for follow-up. Conclusion 4H syndrome is a rare congenital hypomyelinating leukodystrophy inherited as an autosomal recessive disorder due to mutations in the POLR3A and POLR3B gene. Delay or regression of milestones, abnormalities in dentition and endocrinal perturbations are its hallmark. A novel mutation in the POLR3A gene resulting in amino acid substitution of arginine for glutamine at codon 808 (p.R808Q) was detected in exon 18 in our case