Deep clinicopathological phenotyping identifies a previously unrecognized pathogenic EMD splice variant.

Autor:	Calame DG; Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Texas Children's Hospital, Houston, Texas, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Fatih JM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Herman I; Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Texas Children's Hospital, Houston, Texas, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Coban-Akdemir Z; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Du H; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Mitani T; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Jhangiani SN; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, 77030, USA., Marafi D; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, 13110, Kuwait., Gibbs RA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, 77030, USA., Posey JE; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Mehta VP; Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, 77030, USA., Mohila CA; Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, 77030, USA., Abid F; Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Texas Children's Hospital, Houston, Texas, 77030, USA., Lotze TE; Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Texas Children's Hospital, Houston, Texas, 77030, USA., Pehlivan D; Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Texas Children's Hospital, Houston, Texas, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA., Adesina AM; Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, 77030, USA., Lupski JR; Texas Children's Hospital, Houston, Texas, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, 77030, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA.
Jazyk:	angličtina
Zdroj:	Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2021 Oct; Vol. 8 (10), pp. 2052-2058. Date of Electronic Publication: 2021 Sep 15.
DOI:	10.1002/acn3.51454
Abstrakt:	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. (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze:	MEDLINE
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