Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement.
Eur J Med Genet
; 63(2): 103649, 2020 Feb.
Article
en En
| MEDLINE
| ID: mdl-30986545
ABSTRACT
EXOSC3-related autosomal recessive neurodevelopmental disorders are rare entities with variable clinical course and prognosis. They are characterized by hypoplasia of cerebellar structures and pons, degeneration of the anterior horn cells and motor as well as neurocognitive impairment. Phenotypic expression is variable with an overall poor outcome. Current research suggests clear genotype-phenotype correlations among EXOSC3-pathogenic-variants carriers. Homozygosity for the EXOSC3 variant c.395Aâ¯>â¯C, p.(Asp132Ala) is proposed to lead to a rather mild phenotype compared to compound-heterozygous EXOSC3-pathogenic-variants carriers with lethal neurological disease in very early childhood. In this study, we report two siblings (21- and 8-year-old) affected by PCH1B with an unusual presentation. We identified compound heterozygosity for the well-established EXOSC3 variant c.395Aâ¯>â¯C, p.(Asp132Ala) and the novel variant c.572Gâ¯>â¯A, p.(Gly191Asp), expanding the genetic spectrum. Phenotypic presentation of the siblings was strikingly different from that of literature reports with a surprisingly mild disease manifestation and an unexpected intrafamilial variability. This study demonstrates the extensive clinical heterogeneity and the broad phenotypic spectrum associated with EXOSC3-associated disorders. Enlargement of sample sizes and reports of novel cases will be essential for the delineation of associated phenotypes.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades Cerebelosas
/
Proteínas de Unión al ARN
/
Complejo Multienzimático de Ribonucleasas del Exosoma
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Med Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania