Deep clinicopathological phenotyping identifies a previously unrecognized pathogenic EMD splice variant
| Autor: | Richard A. Gibbs, Vidya Mehta, Tadahiro Mitani, Shalini N. Jhangiani, James R. Lupski, Isabella Herman, Timothy Lotze, Haowei Du, Zeynep Coban-Akdemir, Davut Pehlivan, Daniel G. Calame, Dana Marafi, Farida Abid, Jawid M Fatih, Jennifer E. Posey, Adekunle M. Adesina, Carrie A. Mohila |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proband
Muscle biopsy medicine.diagnostic_test Case Study business.industry General Neuroscience In silico Alternative splicing Emerin Neurosciences. Biological psychiatry. Neuropsychiatry Computational biology medicine.disease RNA splicing Medicine Neurology (clinical) Neurology. Diseases of the nervous system Muscular dystrophy business RC346-429 Exome sequencing RC321-571 |
| Zdroj: | Annals of Clinical and Translational Neurology Annals of Clinical and Translational Neurology, Vol 8, Iss 10, Pp 2052-2058 (2021) |
| ISSN: | 2328-9503 |
| Popis: | Exome sequencing (ES) has revolutionized rare disease management, yet only ~25%–30% of patients receive a molecular diagnosis. A limiting factor is the quality of available phenotypic data. Here, we describe how deep clinicopathological phenotyping yielded a molecular diagnosis for a 19‐year‐old proband with muscular dystrophy and negative clinical ES. Deep phenotypic analysis identified two critical data points: (1) the absence of emerin protein in muscle biopsy and (2) clinical features consistent with Emery‐Dreifuss muscular dystrophy. Sequencing data analysis uncovered an ultra‐rare, intronic variant in EMD, the gene encoding emerin. The variant, NM_000117.3: c.188‐6A > G, is predicted to impact splicing by in silico tools. This case thus illustrates how better integration of clinicopathologic data into ES analysis can enhance diagnostic yield with implications for clinical practice. |
| Databáze: | OpenAIRE |
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