Singleton-Merten syndrome, a critical and rare multifactorial disorder that is closely linked to R516Q mutation in MDA5 protein associated with an enhanced interferon response in the affected individual. In the present study, we provide conclusive key evidence on R516Q mutation and their connectivity towards sequence-structural basis dysfunction of MDA5 protein. Among the various mutations, we found R516Q is the most pathogenic mutation based on mutational signature Q-A-[RE]-G-R-[GA]-R-A-[ED]-[DE]-S-[ST]-Y-[TSAV]-L-V designed from our work. Further, we derived a distant ortholog for this mutational signature from which we identified 343 intra-residue interactions that fall communally in the position required to maintain the structural and functional integration of protein architecture. This identification served us to understand the critical role of hot spots in residual aggregation that holds a native form of folding conformation in the functional region. In addition, the long-range molecular dynamics simulation demarcated the residual dependencies of conformational transition in distinct regions (L29360-370α18, α19380-410L31, α21430-480L33-α22-L35 and α24510-520L38) occurring upon R516Q mutation. Together, our results emphasise that the dislocation of functional hot spots Pro229, Arg414, Val498, Met510, Ala513, Gly515 and Arg516 in MDA5 protein which is important for interior structural packing and fold arrangements. In a nutshell, our findings are perfectly conceded with other experimental reports and will have potential implications in immune therapeutical advancement for rare singleton-merten syndrome.

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Regional odontodysplasia (RO) is a rare disorder of dental development. The affected teeth are clinically hypoplastic and hypocalcified, presenting a ghost-like appearance radiographically. The aim of this work was to report a clinical case of a child with both primary and permanent dentition affected by RO. The conducted therapy was based on a conservative approach, which consisted of follow-up clinical evaluations of the anomalous teeth. However, the endodontic treatment of the primary incisors failed. Then, the chosen option for patient rehabilitation became extraction followed by removable of prosthesis confection. The extracted teeth were processed for histological analysis. In spite of the uncertain prognosis, but taking into account the psychological aspects of the patient, a conservative approach in an attempt to maintain those viable teeth in the oral cavity should be established.

The purpose of the study was to analyze the radiographic features of segmental odontomaxillary dysplasia by studying the radiographs of 12 new cases. With a standard data collection form, the radiographic characteristics were assessed by the two principal investigators who studied available radiographs of all cases. As in previously reported cases, abnormal findings in all patients were confined to the posterior segment of one maxilla. The most common findings in the cases studied were sclerosis and thickening of bony trabeculae, missing permanent premolar teeth, abnormal spacing of primary molars vertical orientation of bony trabeculae, a smaller maxillary sinus, and delayed eruption of permanent posterior teeth. Less commonly observed features were enlarged crowns, roots, and pulps of primary molars, irregular resorption of primary molar roots, mediolateral expansion of the alveolar process, splayed roots of primary molars, and an abnormal medial position of the teeth.

Soft-tissue calcifications of the dental follicle in regional odontodysplasia were studied via the correlated techniques of light microscopy, scanning electron microscopy (SEM), calcium x-ray cartography, and high-resolution transmission electron microscopy (TEM). The study revealed several types of calcification, mostly located within an area normally occupied by enamel formation. Some of them are produced without collagen being involved; others result from the mineralization of collagen fibers. Sometimes they were surrounded by a structureless homogeneous zone and resulted from the fusion of several smaller globules. High-resolution TEM revealed two different types of calcifications: a few composed of platelike crystallites, presenting a \"sheath\" characteristic of apatite formation, most of them poorly crystallized. The calcifications were in close contact with the cytoplasm of the neighboring connective tissue cells in which an abundance of microfilaments was found. It is suggested that these filaments might be involved in the formation of dystrophic soft-tissue calcifications.

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