Genetic analysis of five pedigrees affected with multiple osteochondromas.
10.3760/cma.j.issn.1003-9406.2020.07.004
- Author:
Ying BAI
1
;
Zhihui JIAO
;
Ning LIU
;
Shuang HU
;
Kaihui ZHAO
;
Xiangdong KONG
Author Information
1. Center of Prenatal Diagnosis, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. kongxd@263.net.
- Publication Type:Journal Article
- From:
Chinese Journal of Medical Genetics
2020;37(7):717-720
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To detect variants of EXT1 and EXT2 genes among five pedigrees affected with multiple osteochondromas and provide prenatal diagnosis for the families based on the results.
METHODS:The EXT1 and EXT2 genes of the probands were analyzed by targeted next generation sequencing (NGS). Suspected pathological variants were validated by Sanger sequencing in the probands, their family members and 200 unrelated healthy controls. Multiple ligation-dependent probe amplification (MLPA) was used to confirm the presence of gross deletions. Prenatal diagnosis was provided for 2 couples carrying pathogenic or likely pathogenic variants.
RESULTS:Five variants were detected in the pedigrees, which included EXT1 exon 2-3 deletion, c.1468dupC (p.Leu490ProfsX31), c.2084delC (p.Pro695LeufsX11), and EXT2 c.187delT (p.Phe63SerfsX29) and c.1362T>G (p.Tyr454X). Among these, EXT1 exon 2-3 deletion, c.2084delC (p.Pro695LeufsX11) and EXT2 c.187delT (p.Phe63SerfsX29) were unreported previously. The three novel variants were not found among unaffected members of the pedigree and the 200 healthy controls. Upon prenatal diagnosis, the two fetuses were found to carry the same variants of the the probands.
CONCLUSION:Pathological variants of the EXT1 and EXT2 genes probably underlie the multiple osteochondromas among the 5 pedigrees. Prenatal diagnosis based on the results can effectively reduce the birth of further offspring affected with the disease.
