Diagnostic Yield of Whole Genome Sequencing After Nondiagnostic Exome Sequencing or Gene Panel in Developmental and Epileptic Encephalopathies.
Neurology
; 96(13): e1770-e1782, 2021 03 30.
Article
em En
| MEDLINE
| ID: mdl-33568551
ABSTRACT
OBJECTIVE:
To assess the benefits and limitations of whole genome sequencing (WGS) compared to exome sequencing (ES) or multigene panel (MGP) in the molecular diagnosis of developmental and epileptic encephalopathies (DEE).METHODS:
We performed WGS of 30 comprehensively phenotyped DEE patient trios that were undiagnosed after first-tier testing, including chromosomal microarray and either research ES (n = 15) or diagnostic MGP (n = 15).RESULTS:
Eight diagnoses were made in the 15 individuals who received prior ES (53%) 3 individuals had complex structural variants; 5 had ES-detectable variants, which now had additional evidence for pathogenicity. Eleven diagnoses were made in the 15 MGP-negative individuals (68%); the majority (n = 10) involved genes not included in the panel, particularly in individuals with postneonatal onset of seizures and those with more complex presentations including movement disorders, dysmorphic features, or multiorgan involvement. A total of 42% of diagnoses were autosomal recessive or X-chromosome linked.CONCLUSION:
WGS was able to improve diagnostic yield over ES primarily through the detection of complex structural variants (n = 3). The higher diagnostic yield was otherwise better attributed to the power of re-analysis rather than inherent advantages of the WGS platform. Additional research is required to assist in the assessment of pathogenicity of novel noncoding and complex structural variants and further improve diagnostic yield for patients with DEE and other neurogenetic disorders.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espasmos Infantis
/
Sequenciamento Completo do Genoma
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Sequenciamento do Exoma
Tipo de estudo:
Diagnostic_studies
Limite:
Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Neurology
Ano de publicação:
2021
Tipo de documento:
Article