Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2023

Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects

Nicole Siddall
Liang Zhao
Josephine Bowles
Ralf Schittenhelm
Cheng Huang
Gary Hime

Résumé

Squamous cell carcinoma antigen recognized by T cells 3 ( SART3 ) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Collectively, these findings suggest that bi-allelic SART3 variants underlie a spliceosomopathy which we tentatively propose be termed INDYGON syndrome ( I ntellectual disability, N eurodevelopmental defects and D evelopmental delay with 46,X Y GON adal dysgenesis). Our findings will enable additional diagnoses and improved outcomes for individuals born with this condition.
Fichier principal
Vignette du fichier
s41467-023-39040-0.pdf (2.37 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Licence : CC BY - Paternité

Dates et versions

hal-04150348 , version 1 (05-07-2023)

Licence

Paternité

Identifiants

Citer

Katie Ayers, Stefanie Eggers, Ben Rollo, Katherine Smith, Nadia Davidson, et al.. Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects. Nature Communications, 2023, 14 (1), pp.3403. ⟨10.1038/s41467-023-39040-0⟩. ⟨hal-04150348⟩
22 Consultations
34 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More