Analysis of clinical phenotype and genetic variant in a Chinese pedigree affected with cleidocranial dysplasia.
10.3760/cma.j.cn511374-20211024-00845
- VernacularTitle:一个颅骨锁骨发育不全家系的临床表型及遗传学分析
- Author:
Yinhua CHEN
1
;
Haibin GU
;
Genxiong TANG
;
Rong LI
Author Information
1. Department of Child Health Care, the Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China. 15850780062@163.com.
- Publication Type:Journal Article
- MeSH:
Humans;
Pregnancy;
Female;
Cleidocranial Dysplasia/genetics*;
Pedigree;
Core Binding Factor Alpha 1 Subunit/genetics*;
Phenotype;
China;
Mutation
- From:
Chinese Journal of Medical Genetics
2022;39(11):1247-1251
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical features and pathogenic variant in a Chinese pedigree affected with cleidocranial dysplasia (CCD).
METHODS:Clinical data of 8 patients from the pedigree was collected, including physical examination and X-ray images of head, face, spine, limbs, and mouth. Peripheral blood samples were collected from 6 affected members for the extraction of genomic DNA. The proband and other 3 patients were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing of the other 2 affected members from the pedigree.
RESULTS:This pedigree has included 22 members (8 affected) from four generations. Genetic testing revealed that the proband has harbored a novel pathogenic variant of the RUNX2 gene [NM_001024630: c.1268_1277del (p.P425Afs*56)], which was inherited from her mother and carried by all affected members in the pedigree. The same variant was not detected among the unaffected members, suggesting co-segregation with the phenotype.
CONCLUSION:The c.1268_1277del (p.P425Afs*56) variant of the RUNX2 gene probably underlay the pathogenesis of CCD in this pedigree. Genetic testing has facilitated the definite diagnosis and enabled prenatal diagnosis.
