A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia

Pathogenic genes in most patients with cleidocranial dysplasia have been confirmed to be runt-related transcription factor 2 (RUNX2), which controls mutations in specific osteoblast transcription factors and affects skull ossification and suture adhesion. This study aimed to explore the role of RUNX...

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Main Authors: Jing Wang, Qiuying Li, Hongyu Li, Xiu Liu, Ying Hu, Yuxing Bai, Kai Yang
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024163086
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author Jing Wang
Qiuying Li
Hongyu Li
Xiu Liu
Ying Hu
Yuxing Bai
Kai Yang
author_facet Jing Wang
Qiuying Li
Hongyu Li
Xiu Liu
Ying Hu
Yuxing Bai
Kai Yang
author_sort Jing Wang
collection DOAJ
description Pathogenic genes in most patients with cleidocranial dysplasia have been confirmed to be runt-related transcription factor 2 (RUNX2), which controls mutations in specific osteoblast transcription factors and affects skull ossification and suture adhesion. This study aimed to explore the role of RUNX2 mutations. Here, we report a rare case of a splice site mutation in a Chinese population with typical cleidocranial dysplasia symptoms, cranial suture insufficiency, clavicle dysplasia, and dental anomalies. Peripheral blood samples from the proband and her mother were subjected to Sanger sequencing. The expression levels of RUNX2 before and after mutation were verified using digital PCR (dPCR). The results revealed a classic mutation at the fifth base of the intron 5 initiation splicing sequence (NM001024630.4: C.685+5G > A). The mutation rate in the proband was 53 %, while the mother did not have any mutations. The secondary RNA structure of the RUNX2 gene in the progenitor was predicted to change, and the structural free energy was low in the wild-type, with the stem folded first and the structure being relatively stable. After the mutation, the free energy increased. This finding enriches the RUNX2 mutation library of CD-related genes in Chinese individuals.
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publishDate 2024-11-01
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series Heliyon
spelling doaj-art-6ae19b42480c4e6bb9d515aa42a2e0212025-08-20T02:07:31ZengElsevierHeliyon2405-84402024-11-011022e4027710.1016/j.heliyon.2024.e40277A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasiaJing Wang0Qiuying Li1Hongyu Li2Xiu Liu3Ying Hu4Yuxing Bai5Kai Yang6Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, No.4 Tiantan Xili, Dong cheng District, Beijing, 100050, ChinaDepartment of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, No.4 Tiantan Xili, Dong cheng District, Beijing, 100050, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China; Department of Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, ChinaDepartment of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, No.4 Tiantan Xili, Dong cheng District, Beijing, 100050, ChinaDepartment of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, No.4 Tiantan Xili, Dong cheng District, Beijing, 100050, China; Corresponding author.Pathogenic genes in most patients with cleidocranial dysplasia have been confirmed to be runt-related transcription factor 2 (RUNX2), which controls mutations in specific osteoblast transcription factors and affects skull ossification and suture adhesion. This study aimed to explore the role of RUNX2 mutations. Here, we report a rare case of a splice site mutation in a Chinese population with typical cleidocranial dysplasia symptoms, cranial suture insufficiency, clavicle dysplasia, and dental anomalies. Peripheral blood samples from the proband and her mother were subjected to Sanger sequencing. The expression levels of RUNX2 before and after mutation were verified using digital PCR (dPCR). The results revealed a classic mutation at the fifth base of the intron 5 initiation splicing sequence (NM001024630.4: C.685+5G > A). The mutation rate in the proband was 53 %, while the mother did not have any mutations. The secondary RNA structure of the RUNX2 gene in the progenitor was predicted to change, and the structural free energy was low in the wild-type, with the stem folded first and the structure being relatively stable. After the mutation, the free energy increased. This finding enriches the RUNX2 mutation library of CD-related genes in Chinese individuals.http://www.sciencedirect.com/science/article/pii/S2405844024163086Cleidocranial dysplasiaRUNX2Splice-site mutationDPCRChinese population
spellingShingle Jing Wang
Qiuying Li
Hongyu Li
Xiu Liu
Ying Hu
Yuxing Bai
Kai Yang
A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia
Heliyon
Cleidocranial dysplasia
RUNX2
Splice-site mutation
DPCR
Chinese population
title A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia
title_full A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia
title_fullStr A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia
title_full_unstemmed A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia
title_short A novel RUNX2 splice site mutation in Chinese associated with cleidocranial dysplasia
title_sort novel runx2 splice site mutation in chinese associated with cleidocranial dysplasia
topic Cleidocranial dysplasia
RUNX2
Splice-site mutation
DPCR
Chinese population
url http://www.sciencedirect.com/science/article/pii/S2405844024163086
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