To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from Pakistan). Overall, 701 pathogenic/likely pathogenic unique SNVs and 40 CNVs were identified. In 620 patients, the result of the biochemical tests guided variant classification and reporting. Top five diagnosed diseases were: Gaucher disease, Niemann-Pick disease type A/B, phenylketonuria, mucopolysaccharidosis type I, and Wilson disease. We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. More importantly, up to 43% of these patients (n = 610) could benefit from medical treatments (e.g., enzyme replacement therapy). This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs.
Nanoparticles based on noble metals such as gold are characterized by their surface plasmon resonance (SPR). Aggregation of gold nanoparticles causes an interparticle plasmon coupling, which can be observed as a redshift in the maximum absorbance. This behavior is employed in the presented work to detect antibodies in human sera samples. Analysis of Lyme borreliosis is considered as a model in the here case. Therefore, gold nanoparticles are synthesized and modified with two proteins, surface VlsE Borrelia antigen and protein A. The specific interaction of the two proteins with anti-Borrelia antibodies result in aggregation of the gold nanoparticles. Three different sizes (20, 30, and 40 nm) are tested; a convenient recognition of antibodies is achieved with all sizes using spectroscopic measurements. In addition, 30 nm particles show a very promising colorimetric detection; accumulation of nanoparticles could be easily observed using naked eyes. The size of the modified particles show a crucial impact on the assay time; 3 h, 30 min, and 1 min as incubation time, are needed to obtain considered results when 20, 30, and 40 nm particles are used, respectively. The proposed test can be performed only in one step with no additional washing steps, making it advantageous over the other conventional methods. The test is promising, simple, and suitable for point-of-care testing. Applying of the proposed platform to other assays is suggested for rapid analysis.
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