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Title: Evaluating systematic reanalysis of clinical genomic data in rare disease from single center experience and literature review.
Austin Authors: Tan, Natalie B;Stapleton, Rachel;Stark, Zornitza;Delatycki, Martin B ;Yeung, Alison;Hunter, Matthew F;Amor, David J;Brown, Natasha J;Stutterd, Chloe A ;McGillivray, George;Yap, Patrick;Regan, Matthew;Chong, Belinda;Fanjul Fernandez, Miriam;Marum, Justine;Phelan, Dean;Pais, Lynn S;White, Susan M;Lunke, Sebastian;Tan, Tiong Y
Affiliation: Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
Broad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
Genetic Health Service NZ, Auckland, New Zealand
Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
Clinical Genetics
Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC, Australia
Royal Children's Hospital, Parkville, VIC, Australia
Department of Paediatrics, Monash University, Clayton, VIC, Australia
Monash Genetics, Monash Health, Clayton, VIC, Australia
Murdoch Children's Research Institute, Melbourne, VIC, Australia
Issue Date: Nov-2020
Date: 2020-09-23
Publication information: Molecular Genetics & Genomic Medicine 2020; 8(11): e1508
Abstract: Our primary aim was to evaluate the systematic reanalysis of singleton exome sequencing (ES) data for unsolved cases referred for any indication. A secondary objective was to undertake a literature review of studies examining the reanalysis of genomic data from unsolved cases. We examined data from 58 unsolved cases referred between June 2016 and March 2017. First reanalysis at 4-13 months after the initial report considered genes newly associated with disease since the original analysis; second reanalysis at 9-18 months considered all disease-associated genes. At 25-34 months we reviewed all cases and the strategies which solved them. Reanalysis of existing ES data alone at two timepoints did not yield new diagnoses. Over the same timeframe, 10 new diagnoses were obtained (17%) from additional strategies, such as microarray detection of copy number variation, repeat sequencing to improve coverage, and trio sequencing. Twenty-seven peer-reviewed articles were identified on the literature review, with a median new diagnosis rate via reanalysis of 15% and median reanalysis timeframe of 22 months. Our findings suggest that an interval of greater than 18 months from the original report may be optimal for reanalysis. We also recommend a multi-faceted strategy for cases remaining unsolved after singleton ES.
DOI: 10.1002/mgg3.1508
ORCID: 0000-0003-3339-7342
Journal: Molecular Genetics & Genomic Medicine
PubMed URL: 32969205
Type: Journal Article
Subjects: exome sequencing
genome sequencing
rare disease
Appears in Collections:Journal articles

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