Loss-of-function mutations in FGF8 can be independent risk factors for holoprosencephaly.
Hum Mol Genet
; 27(11): 1989-1998, 2018 06 01.
Article
en En
| MEDLINE
| ID: mdl-29584859
ABSTRACT
The utilization of next generation sequencing has been shown to accelerate gene discovery in human disease. However, our confidence in the correct disease-associations of rare variants continues to depend on functional analysis. Here, we employ a sensitive assay of human FGF8 variants in zebrafish to demonstrate that the spectrum of isoforms of FGF8 produced by alternative splicing can provide key insights into the genetic susceptibility to human malformations. In addition, we describe novel mutations in the FGF core structure that have both subtle and profound effects on ligand posttranslational processing and biological activity. Finally, we solve a case of apparent digenic inheritance of novel variants in SHH and FGF8, two genes known to functionally coregulate each other in the developing forebrain, as a simpler case of FGF8 diminished function.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Holoprosencefalia
/
Empalme Alternativo
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Proteínas de Pez Cebra
/
Factor 8 de Crecimiento de Fibroblastos
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Factores de Crecimiento de Fibroblastos
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article