Clinical and molecular delineation of PUS3-associated neurodevelopmental disorders

Miriam Nøstvik, Sarah M. Kateta, Bitten Schönewolf-Greulich, Alexandra Afenjar, Magalie Barth, Felix Boschann, Diane Doummar, Tobias B. Haack, Boris Keren, Ludmilla A. Livshits, Davide Mei, Joohyun Park, Tiziana Pisano, Clement Prouteau, Muhammad Umair, Ahmed Waqas, Alban Ziegler, Renzo Guerrini, Rikke S. Møller, Zeynep Tümer*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


Biallelic variants in PUS3 have recently been recognized as a rare cause of neurodevelopmental disorders. Pseudouridine synthase-3 encoded by PUS3 is an enzyme important for modification of various RNAs, including transfer RNA (tRNA). Here we present the clinical and genetic features of 21 individuals with biallelic PUS3 variants: seven new and 14 previously reported individuals, where clinical features of two were updated. The clinical and genetic information were collected through collaborations or by literature search. All individuals were characterized by the local clinicians and the gene variants were identified by next generation sequencing (NGS) based methodologies. The clinical picture was dominated by global developmental delay, epilepsy, hypotonia and microcephaly. Gray sclera, which has previously been suggested to be a characteristic feature of PUS3-associated phenotypes, was reported in only seven individuals. The patients had some dysmorphic facial features, but a recognizable gestalt was not observed. In conclusion, homozygous and compound heterozygous PUS3 variants lead to a rare neurodevelopmental disorder. Further functional studies are necessary to understand involvement of PUS3 and tRNA biogenesis in normal and abnormal brain development.

TidsskriftClinical Genetics
Udgave nummer5
Sider (fra-til)628-633
StatusUdgivet - nov. 2021

Bibliografisk note

Funding Information:
DFG, German Research Foundation, Grant/Award Numbers: 418081722, 433158657; Improving Diagnoses of Mental Retardation in Children in Eastern Europe and Central Asia through Genetic Characterisation and Bioinformatics/Statistics 2009‐2012, Grant/Award Number: Grant Agreement n. 223692; Tuscany Region Call for Health 2018, Grant/Award Number: grant DECODE‐EE Funding information

Funding Information:
The authors thank the patients and their families for their participation in this study. T.B.H. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—418081722, 433158657; LAL was supported by «Improving Diagnoses of Mental Retardation in Children in Eastern Europe and Central Asia through Genetic Characterisation and Bioinformatics/Statistics» 2009–2012, Grant Agreement n. 223692, CHERISH; RG's work was funded by the Tuscany Region Call for Health 2018 (grant DECODE‐EE).

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


Dyk ned i forskningsemnerne om 'Clinical and molecular delineation of PUS3-associated neurodevelopmental disorders'. Sammen danner de et unikt fingeraftryk.