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DECIPHER (Database of Genomic Variation and Phenotype in Humans Using Ensembl Resources) shares candidate diagnostic variants and phenotypic data from patients with genetic disorders to facilitate research and improve the diagnosis, management, and therapy of rare diseases. The platform sits at the boundary between genomic research and the clinical community. DECIPHER aims to ensure that the most up-to-date data are made rapidly available within its interpretation interfaces to improve clinical care. Newly integrated cardiac case–control data that provide evidence of gene–disease associations and inform variant interpretation exemplify this mission. New research resources are presented in a format optimized for use by a broad range of professionals supporting the delivery of genomic medicine. The interfaces within DECIPHER integrate and contextualize variant and phenotypic data, helping to determine a robust clinico-molecular diagnosis for rare-disease patients, which combines both variant classification and clinical fit. DECIPHER supports discovery research, connecting individuals within the rare-disease community to pursue hypothesis-driven research. [ABSTRACT FROM AUTHOR]

This paper aims to establish a link between the felt quality in musical expression and the psycho-somatic structure of the person playing. This includes specific areas of the body, a corresponding set of emotions and thought patterns, as well as the deeper needs of the person. Discernment of felt quality is facilitated by using the symbolic reference system of the five Indian and Greek elements earth, water, fire, air and space. This framework not only enables the therapist to locate a client's limitations or blockages, but also a means of understanding how to work on them, thus ultimately improving their musicality and well-being. The findings are drawn from the author's work as a music-therapist with adult clients as well as with young autistic, psychotic and disharmonic children, aged 2-8 in a day clinic in central France. Within that work, strong evidence has been found for seven major neuro-musical thresholds, that, when worked on, can bring about substantial changes in a person. [ABSTRACT FROM AUTHOR]

BACKGROUND Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits. METHODS We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland. Standardized phenotypic data were collected, and exome sequencing and microarray analyses were performed to investigate novel genetic causes. We developed an iterative variant analysis pipeline and reported candidate variants to clinical teams for validation and diagnostic interpretation to inform communication with families. Multiple regression analyses were performed to evaluate factors affecting the probability of diagnosis. RESULTS A total of 13,449 probands were included in the analyses. On average, we reported 1.0 candidate variant per parent–offspring trio and 2.5 variants per singleton proband. Using clinical and computational approaches to variant classification, we made a diagnosis in approximately 41% of probands (5502 of 13,449). Of 3599 probands in trios who received a diagnosis by clinical assertion, approximately 76% had a pathogenic de novo variant. Another 22% of probands (2997 of 13,449) had variants of uncertain significance in genes that were strongly linked to monogenic developmental disorders. Recruitment in a parent–offspring trio had the largest effect on the probability of diagnosis (odds ratio, 4.70; 95% confidence interval [CI], 4.16 to 5.31). Probands were less likely to receive a diagnosis if they were born extremely prematurely (i.e., 22 to 27 weeks’ gestation; odds ratio, 0.39; 95% CI, 0.22 to 0.68), had in utero exposure to antiepileptic medications (odds ratio, 0.44; 95% CI, 0.29 to 0.67), had mothers with diabetes (odds ratio, 0.52; 95% CI, 0.41 to 0.67), or were of African ancestry (odds ratio, 0.51; 95% CI, 0.31 to 0.78). CONCLUSIONS Among probands with severe, probably monogenic, difficult-to-diagnose developmental disorders, multimodal analysis of genomewide data had good diagnostic power, even after previous attempts at diagnosis. (Funded by the Health Innovation Challenge Fund and Wellcome Sanger Institute.) [ABSTRACT FROM AUTHOR]