Open AccessEvaluating systematic reanalysis of clinical genomic data in rare disease from single center experience and literature review
Author(s) -
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.
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1508
Subject(s) - medical diagnosis , exome sequencing , medicine , disease , copy number variation , exome , rare disease , pediatrics , genome , gene , genetics , pathology , biology , phenotype
Background 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. Methods 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. Results 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. Conclusion 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.