Hidden etiology of cerebral palsy: genetic and clinical heterogeneity and efficient diagnosis by next-generation sequencing.

Fecha de publicación: 11/11/2020 Fecha Ahead of Print: 11/11/2020

Autores de IIS La Fe

Grupos

Investigación Traslacional en Genética

Leader

Francisco Martínez Castellano

Abstract

Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent research studies focused on genetic diagnosis in patients with CP of unknown etiology. The present study was carried out in 20 families with one family member affected with idiopathic CP. Chromosomal microarray and exome sequencing techniques were performed in all patients. Chromosomal microarray analysis did not show any pathological or probable pathological structural variant. However, the next-generation sequencing study showed a high diagnostic yield. We report 11/20 patients (55%) with different pathogenic or potentially pathogenic variants detected by exome sequencing analysis: five patients with mutations in genes related to hereditary spastic paraplegia, two with mutations in genes related to Aicardi-Goutières syndrome, three with mutations in genes related to developmental/epileptic encephalopathies, and one with a mutation in the PGK1 gene. The accurate and precise patients' selection, the use of a high-throughput genetic platform, the selection of adequate target genes, and the application of rigorous criteria for the clinical interpretation are the most important elements for a good diagnostic performance. Based on our findings, next-generation sequencing should be considered in patients with cryptogenic CP as the first line of genetic workup. IMPACT: Sequencing techniques in CP of uncertain etiology provides a diagnostic yield of 55%. The appropriate selection of cases optimizes the diagnostic yield. NGS facilitate better understanding of new phenotypes of certain genetic diseases.

Datos de la publicación

ISSN/ISSNe:: 0031-3998, 1530-0447
Tipo:: Review
Páginas:: 284-288
DOI:: 10.1038/s41390-020-01250-3
Factor de Impacto:: 1,056 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Rosello M:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Caro-Llopis A:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Orellana C:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Oltra S:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Alemany-Albert M:: Neuropediatric Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Marco-Hernandez AV:: Neuropediatric Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Monfort S:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Pedrola L:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Martinez F:: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Tomás M:: Neuropediatric Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain