1例颅骨锁骨发育不全家系临床表型及基因突变分析

doi:10.13591/j.cnki.kqyx.2026.01.009

口腔医学 ›› 2026, Vol. 46 ›› Issue (1): 54-60.doi: 10.13591/j.cnki.kqyx.2026.01.009

1例颅骨锁骨发育不全家系临床表型及基因突变分析

张欣瑜¹^,²^,³, 冒纪¹^,²^,³, 程婷婷¹^,²^,³, 马兰¹^,³, 程礼明⁴(), 潘永初¹^,²^,³()

1 口腔疾病研究与防治国家级重点实验室培育建设点,江苏南京(210029)
2 南京医科大学附属口腔医院正畸科,江苏南京(210029)
3 江苏省口腔转化医学工程研究中心,江苏南京(210029)
4 常州市中医医院口腔正畸科,江苏常州(213003)

收稿日期:2025-04-28 出版日期:2026-01-28 发布日期:2026-01-16
通讯作者: 程礼明,潘永初 E-mail:nuonuo1220@hotmail.com;panyongchu@njmu.edu.cn
基金资助:
江苏省科教兴省能力提升工程——江苏省研究型医院培育项目(YJXYYJSDW4);江苏省医学创新中心(CXZX202227)

Clinical and genetic study on a cleidocranial dysplasia family

ZHANG Xinyu¹^,²^,³, MAO Ji¹^,²^,³, CHENG Tingting¹^,²^,³, MA Lan¹^,³, CHENG Liming⁴(), PAN Yongchu¹^,²^,³()

State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing 210029, China

Received:2025-04-28 Online:2026-01-28 Published:2026-01-16
Contact: CHENG Liming, PAN Yongchu E-mail:nuonuo1220@hotmail.com;panyongchu@njmu.edu.cn

摘要/Abstract

摘要：

目的检测1例颅骨锁骨发育不全(cleidocranial dysplasia,CCD)家系的基因突变情况,确认突变位点并探究该突变对蛋白结构和功能的影响。方法通过临床症状和影像学检查,确诊1例CCD先证者,抽取该先证者及其家庭成员的外周血进行全外显子组测序并通过Sanger测序确认该先证者的致病突变,对该突变位点导致的蛋白结构功能变化及该基因参与CCD发生的可能机制进行探究。结果该家系中先证者及其父亲均具有锁骨发育不良、囟门未闭合、颌骨及牙齿发育异常等典型的CCD临床表现。测序结果发现了一个既往已报道的RUNX2基因错义突变位点—c.569G>A, p.Arg190Gln,突变发生在高度保守的runt结构域,影响RUNX2蛋白的功能,生物信息学分析也进一步提示RUNX2在颅颌面骨及牙齿发育过程中发挥重要作用。结论在1例中国CCD家系中发现RUNX2基因第4号外显子区的错义突变位点,从分子生物学水平为CCD患者治疗提供新见解。

关键词: 颅骨锁骨发育不全, RUNX2基因, 错义突变

Abstract:

Objective To confirm the mutation in a family with cleidocranial dysplasia (CCD) and explore its possible effects on protein structure and function. Methods A proband with CCD was diagnosed through clinical symptoms and radiography examinations. Peripheral blood samples were collected from the proband and his family members for whole-exome sequencing. The pathogenic mutation was validated by Sanger sequencing. Further investigations were conducted to analyze the protein structural and functional changes induced by this mutation and explore the potential mechanisms by which this gene contributed to the pathogenesis of CCD. Results In this family, both the proband and his father exhibited typical clinical manifestations of cleidocranial dysplasia (CCD), including clavicular hypoplasia, delayed closure of fontanelles, craniofacial and dental abnormalities. A previously reported RUNX2 missense mutation (c. 569G>A, p. Arg190Gln) was identified in this family. This mutation occurred within the highly conserved runt domain, disrupting RUNX2 protein function. Bioinformatics analysis further confirmed the critical role of RUNX2 in craniofacial skeleton and tooth development. Conclusion A missense mutation in exon 4 of the RUNX2 gene is identified in a Chinese CCD family, providing novel therapeutic insights for CCD patients from molecular biological perspective.

Key words: cleidocranial dysplasia, RUNX2, missense mutation

中图分类号:

R782

张欣瑜, 冒纪, 程婷婷, 马兰, 程礼明, 潘永初. 1例颅骨锁骨发育不全家系临床表型及基因突变分析[J]. 口腔医学, 2026, 46(1): 54-60.

ZHANG Xinyu, MAO Ji, CHENG Tingting, MA Lan, CHENG Liming, PAN Yongchu. Clinical and genetic study on a cleidocranial dysplasia family[J]. Stomatology, 2026, 46(1): 54-60.

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参考文献 29

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测量项目	正常人群^[8]	Ⅰ:1	Ⅱ:1
SNA/(°)	82.8±4.0	90.5	100.2
SNB/(°)	80.1±3.9	90.9	94.2
ANB/(°)	2.7±2.0	-0.4	6.0
NP-FH/(°)	85.4±3.7	101.2	96.3
NA-PA/(°)	6.0±4.4	-3.8	9.3
U1-NA/mm	5.1±2.4	0.5	-4.5
U1-NA/(°)	22.8±5.7	24.3	4.3
L1-NB/mm	6.7±2.1	4.3	0.4
L1-NB/(°)	30.3±5.8	28.6	11.7
U1-L1(°)	124.2±8.2	127.5	158.0
FMA(FH-MP)/(°)	31.1±5.6	13.0	22.6
FMIA(L1-FH)/(°)	54.9±6.1	71.0	83.7
IMPA(L1-MP)/(°)	93.9±6.2	96.0	73.7

1例颅骨锁骨发育不全家系临床表型及基因突变分析

Clinical and genetic study on a cleidocranial dysplasia family

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