Clinical and molecular delineation of PUS3-associated neurodevelopmental disorders
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Clinical and molecular delineation of PUS3-associated neurodevelopmental disorders. / Nøstvik, Miriam; Kateta, Sarah M.; Schönewolf-Greulich, Bitten; Afenjar, Alexandra; Barth, Magalie; Boschann, Felix; Doummar, Diane; Haack, Tobias B.; Keren, Boris; Livshits, Ludmilla A.; Mei, Davide; Park, Joohyun; Pisano, Tiziana; Prouteau, Clement; Umair, Muhammad; Waqas, Ahmed; Ziegler, Alban; Guerrini, Renzo; Møller, Rikke S.; Tümer, Zeynep.
I: Clinical Genetics, Bind 100, Nr. 5, 2021, s. 628-633.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Clinical and molecular delineation of PUS3-associated neurodevelopmental disorders
AU - Nøstvik, Miriam
AU - Kateta, Sarah M.
AU - Schönewolf-Greulich, Bitten
AU - Afenjar, Alexandra
AU - Barth, Magalie
AU - Boschann, Felix
AU - Doummar, Diane
AU - Haack, Tobias B.
AU - Keren, Boris
AU - Livshits, Ludmilla A.
AU - Mei, Davide
AU - Park, Joohyun
AU - Pisano, Tiziana
AU - Prouteau, Clement
AU - Umair, Muhammad
AU - Waqas, Ahmed
AU - Ziegler, Alban
AU - Guerrini, Renzo
AU - Møller, Rikke S.
AU - Tümer, Zeynep
N1 - Publisher Copyright: © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - epilepsy
KW - global developmental delay
KW - intellectual disability
KW - microcephaly
KW - pseudouridine
KW - PUS3
KW - tRNA biogenesis
KW - tRNA modification
U2 - 10.1111/cge.14051
DO - 10.1111/cge.14051
M3 - Journal article
C2 - 34415064
AN - SCOPUS:85113969890
VL - 100
SP - 628
EP - 633
JO - Clinical Genetics
JF - Clinical Genetics
SN - 0009-9163
IS - 5
ER -
ID: 279274997