With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the ‘IndiGen’ program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as ‘IndiGenomes’ http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.

In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations could indeed be recapitulated in the lesional epidermal tissue, including blunting of rete-ridges, thickening of stratum corneum and increase in the size of corneocytes. In addition, we identify marked increase in the putrescine levels due to the elevated expression of spermine/spermidine acetyl transferase. Our study provides insights into the intrinsic self-renewing ability of damaged lesional tissue to restore epidermal functionality in vitiligo.

The severity of acne vulgaris does not correlate with impairment in quality of life.

Hand eczema was particularly common in hospital cleaners and staff with atopic dermatitis. Further studies are needed to address the burden of occupational hand eczema and develop guidelines for its management at a national level.

Summary Background The absence of melanocytes poses a challenge for long‐term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I–II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same. Objectives To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)‐induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets. Methods Genome‐wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next‐generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied. Results Our study found sirtuin1 (SIRT1), an NAD‐dependent deacetylase, to be a direct target of miR‐211 – the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX‐527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR‐211 mimic led to a significant increase in γ‐H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB‐mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR‐211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB‐induced CPDs in primary keratinocytes. Conclusions These findings establish a novel MALAT1–miR‐211–SIRT1 signalling axis that potentially confers protection to the ‘amelanotic’ keratinocytes in vitiligo.

Although the role of noxious α-synuclein (α-SYN) in the degeneration of midbrain dopaminergic neurons and associated motor deficits of Parkinson’s disease is recognized, its impact on non-motor brain circuits and related symptoms remains elusive. Through combining in vivo two-photon imaging with time-coded labelling of neurons in the olfactory bulb of A30P α-SYN transgenic mice, we show impaired growth and branching of dendrites of adult-born granule cells (GCs), with reduced gain and plasticity of dendritic spines. The spine impairments are especially pronounced during the critical phase of integration of new neurons into existing circuits. Functionally, retarded dendritic expansion translates into reduced electrical capacitance with enhanced intrinsic excitability and responsiveness of GCs to depolarizing inputs, while the spine loss correlates with decreased frequency of AMPA-mediated miniature EPSCs. Changes described here are expected to interfere with the functional integration and survival of new GCs into bulbar networks, contributing towards olfactory deficits and related behavioural impairments.

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Aicardi-Gouti eres syndrome type 6 (AGS6) and dyschromatosis symmetrica hereditaria (DSH) are allelic disorders caused respectively by biallelic and heterozygous pathogenic variants in ADAR1. We report three unrelated children presenting with features of both AGS6 and DSH, two of whom had compound heterozygous pathogenic variants in ADAR1. We also describe the novel genetic variants in our cases and review the literature on association of ADAR1-related AGS6 and DSH with these phenotypes.