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Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake. In vitro gain and loss of function studies demonstrate that mitochondrial Ca2+ uniporter (MCU) is crucial for melanogenesis while MCU rheostat, MCUb negatively control melanogenesis. Zebrafish, MCU+/- and MCUb-/- mice models show that MCU complex drives pigmentation in vivo. Mechanistically, MCU silencing activates transcription factor NFAT2 to induce expression of keratin (5, 7, and 8) filaments. Interestingly, keratin5 in turn augments mitochondrial Ca2+ uptake and potentiates melanogenesis by regulating melanosome biogenesis and maturation. Hence this signaling module acts as a negative feedback loop that fine-tunes both mitochondrial Ca2+ signaling and pigmentation. Notably, mitoxantrone, an FDA approved drug that inhibits MCU, reduces pigmentation thereby highlighting therapeutic potential of targeting mitochondrial Ca2+ uptake for clinical management of pigmentary disorders. Taken together, we reveal an MCU-NFAT2-Keratin5 driven signaling axis that acts as a critical determinant of mitochondrial Ca2+ uptake and pigmentation. Given the vital role of mitochondrial Ca2+ signaling and keratin filaments in cellular physiology, this feedback loop could be operational in a variety of other patho-physiological processes. The authors explore the potential role of mitochondrial calcium signaling in vertebrate pigmentation. They show that mitochondrial Ca2+ uniporter (MCU) regulates melanogenesis via the activation of NFAT2 and Keratin 5, and that targeting this signalling axis could be used to treat pigmentary disorders. [ABSTRACT FROM AUTHOR]

Recent advances in the field of genomics have seen the successful implementation of whole exome sequencing as a rapid and efficient diagnostic strategy in several genodermatoses. The aim of this study was to explore the potential of molecular studies in dystrophic epidermolysis bullosa (DEB) in India. Whole exome sequencing was performed using genomic DNA from each case of epidermolysis bullosa, followed by massively parallel sequencing. Resulting reads were mapped to the human reference genome hg19. Sanger sequencing subsequently confirmed the potentially pathogenic mutations. Whole exome sequencing of 18 patients with DEB from 17 unrelated Indian families revealed 20 distinct sequence variants in the COL7A1 gene including 2 widely prevalent mutations. Dominant inheritance was seen in 7 patients, while 11 patients showed a highly variable recessive DEB. This preliminary study using exome sequencing is clearly encouraging and will serve as the basis for future large-scale molecular studies to actively identify and understand DEB in the Indian population. [ABSTRACT FROM AUTHOR]

Infantile hemangiomas (IH) are common vascular tumours. IH have a characteristic natural course. They proliferate rapidly during the early infantile period followed by a period of gradual regression over several years. Most of the uncomplicated IH undergo spontaneous involution, with a small proportion of cases requiring intervention. These are children with IH in life-threatening locations, local complications like haemorrhage, ulceration and necrosis and functional or cosmetic disfigurements. Systemic corticosteroids have been the first line of treatment for many years. Recently, non-selective beta-blockers, such as oral propranalol and topical timolol, have emerged as promising and safer therapies. Other treatment options include interferon and vincristine which are reserved for life-threatening haemangiomas that are unresponsive to conventional therapy. This review mainly focuses on the current trends and evidence-based approach in the management of IH. [ABSTRACT FROM AUTHOR]

Background: Epidermolysis bullosa (EB) has profound effect on the subjective distress, family burden, and quality of life (QOL) of the primary caregivers (PCG). Knowledgeable PCG can efficiently manage children with these skin diseases and also improve their QOL., Objectives: To assess the subjective distress, family burden, and QOL, to develop and assess the short-term effectiveness of a psycho-dermatological education package (PDEP) for the PCG of children with EB., Methods: In this interventional study, 30 PCG of EB were assessed for subjective distress, family burden, and QOL. PDEP, a structured educational tool explaining the disease and its care and stress management, was developed by the authors for the PCG and administered to them after one month of enrolment. They were reassessed after three months and compared with the baseline assessment scores. For comparison, 37 PCG of CI were also studied., Results: The mean age (years) of the subjects was 28.7 ± 6.7 for EB and 30.5 ± 4.6 for CI. The mean or median (range) baseline scores for subjective distress, family burden and QOL of PCG ( n = 20) of EB were 8.4 ± 7.9, 6.5 (0-30); 28.5 ± 17.5, 24 (7-77) and 12.6 ± 6.7, 11.5 (4-28) and for PCG ( n = 14) of CI were 12 ± 4.3, 38.9 ± 16.2 and 17.7 ± 3.6 respectively. The PDEP improved the QOL (p = 0.01), knowledge (p < 0.01) and practices (p < 0.001) for PCG of EB and it improved subjective distress (p < 0.001), QOL (p < 0.01) and knowledge (p < 0.01) for PCG of CI., Conclusions: PDEP is an effective educational tool in improving the QOL and knowledge of PCG, which in turn provides efficient management and psychological support to children affected with EB and CI. It should, therefore, be routinely used for educating the PCG of children with EB and CI., Competing Interests: There are no conflicts of interest. Note: Detailed Questionnaires / Screening Chart and such informations can be obtained on request to the corresponding author., (Copyright: © 2021 Indian Dermatology Online Journal.)