The morbid genome of ciliopathies: an update.
Genet Med
; 22(6): 1051-1060, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-32055034
ABSTRACT
PURPOSE:
Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly.METHODS:
Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes.RESULTS:
In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet-Biedl syndrome.CONCLUSION:
In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Bardet-Biedl
/
Ciliopatías
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article