Identification of a novel de novo PUF60 variant causing Verheij syndrome in a fetus
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Verheij syndrome (VRJS) is a craniofacial spliceosomopathy with a wide phenotypic spectrum. Haploinsufficiency of the poly-uridine binding splicing factor 60 gene (PUF60) and its loss-of-function (LOF) variants are involved in VRJS. We evaluated a human fetus with congenital heart defects and preaxial polydactyly. Clinical data were obtained from the medical record. Whole-exome sequencing (WES) was used to explore the potential genetic etiology, and the detected variant verified using Sanger sequencing. Functional studies were performed to validate the pathogenic effects of the variant. Using trio-WES, we identified a novel PUF60 variant (NM_078480.2; c.1678 T > A, p.*560Argext*204) in the pedigree. Bioinformatic analyses revealed that the variant is potentially pathogenic, and functional studies indicated that it leads to degradation of the elongated protein and subsequently PUF60 LOF, producing some VRJS phenotypes. These findings confirmed the pathogenicity of the variant. This study implicates PUF60 LOF in the etiopathogenesis of VRJS. It not only expands the PUF60 variant spectrum, and also provides a basis for genetic counseling and the diagnosis of VRJS. Although trio-WES is a well-established approach for identifying the genetic etiology of rare multisystemic conditions, functional studies could aid in verifying the pathogenicity of novel variants.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:897 |
---|---|
Enthalten in: |
Gene - 897(2024) vom: 01. Feb., Seite 148092 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Miao, Mingzhu [VerfasserIn] |
---|
Links: |
---|
Themen: |
Journal Article |
---|
Anmerkungen: |
Date Completed 05.02.2024 Date Revised 05.02.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.gene.2023.148092 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM366007386 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM366007386 | ||
003 | DE-627 | ||
005 | 20240205231958.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231227s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.gene.2023.148092 |2 doi | |
028 | 5 | 2 | |a pubmed24n1281.xml |
035 | |a (DE-627)NLM366007386 | ||
035 | |a (NLM)38110042 | ||
035 | |a (PII)S0378-1119(23)00933-2 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Miao, Mingzhu |e verfasserin |4 aut | |
245 | 1 | 0 | |a Identification of a novel de novo PUF60 variant causing Verheij syndrome in a fetus |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 05.02.2024 | ||
500 | |a Date Revised 05.02.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
520 | |a Verheij syndrome (VRJS) is a craniofacial spliceosomopathy with a wide phenotypic spectrum. Haploinsufficiency of the poly-uridine binding splicing factor 60 gene (PUF60) and its loss-of-function (LOF) variants are involved in VRJS. We evaluated a human fetus with congenital heart defects and preaxial polydactyly. Clinical data were obtained from the medical record. Whole-exome sequencing (WES) was used to explore the potential genetic etiology, and the detected variant verified using Sanger sequencing. Functional studies were performed to validate the pathogenic effects of the variant. Using trio-WES, we identified a novel PUF60 variant (NM_078480.2; c.1678 T > A, p.*560Argext*204) in the pedigree. Bioinformatic analyses revealed that the variant is potentially pathogenic, and functional studies indicated that it leads to degradation of the elongated protein and subsequently PUF60 LOF, producing some VRJS phenotypes. These findings confirmed the pathogenicity of the variant. This study implicates PUF60 LOF in the etiopathogenesis of VRJS. It not only expands the PUF60 variant spectrum, and also provides a basis for genetic counseling and the diagnosis of VRJS. Although trio-WES is a well-established approach for identifying the genetic etiology of rare multisystemic conditions, functional studies could aid in verifying the pathogenicity of novel variants | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a PUF60 | |
650 | 4 | |a Prenatal diagnosis | |
650 | 4 | |a Verheij syndrome | |
650 | 4 | |a Whole-exome sequencing | |
650 | 7 | |a RNA Splicing Factors |2 NLM | |
650 | 7 | |a poly-U binding splicing factor 60KDa |2 NLM | |
700 | 1 | |a Wang, Jue |e verfasserin |4 aut | |
700 | 1 | |a Guo, Chenyan |e verfasserin |4 aut | |
700 | 1 | |a Su, Xiaotian |e verfasserin |4 aut | |
700 | 1 | |a Sun, Lizhou |e verfasserin |4 aut | |
700 | 1 | |a Lu, Shoulian |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Gene |d 1979 |g 897(2024) vom: 01. Feb., Seite 148092 |w (DE-627)NLM000233951 |x 1879-0038 |7 nnns |
773 | 1 | 8 | |g volume:897 |g year:2024 |g day:01 |g month:02 |g pages:148092 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.gene.2023.148092 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 897 |j 2024 |b 01 |c 02 |h 148092 |