Evaluating systematic reanalysis of clinical genomic data in rare disease from single center experience and literature review.
Mol Genet Genomic Med
; 8(11): e1508, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32969205
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Testes Genéticos
/
Análise de Sequência de DNA
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Doenças Raras
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Sequenciamento do Exoma
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Austrália