Genetic mutation analysis in two Chinese pedigrees affected with hereditary synpolydactyly
10.3760/cma.j.cn114453-20221019-00327
- VernacularTitle:两个遗传性并多指(趾)家系致病基因突变分析
- Author:
Baoju JI
1
;
Wei WANG
;
Liangqian JIANG
;
Lin LI
;
Xiangyu ZHAO
;
Chunhai GAO
Author Information
1. 临沂市人民医院检验医学中心 临沂市检验医学重点实验室，临沂 276000
- Keywords:
Mutation;
Synpolydactyly;
Homeobox D13 gene;
Whole exome sequencing;
Genetic consulting
- From:
Chinese Journal of Plastic Surgery
2023;39(5):529-534
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the pathogenic gene of the two pedigrees with hereditary synpolydactyly.Methods:Clinical data of two families admitted to the Linyi People’s Hospital due to hereditary synpolydactyly in January 2019 and December 2020 were recruited. Peripheral blood samples were collected and genomic DNAs were extracted. Whole exome sequencing was conducted to detect the pathological mutations and Sanger sequencing was used to verify the variants. The pathogenicity of the mutations was predicted according to PolyPhen-2, PROVEAN and the American College of Medical Genetics and Genomics (ACMG) guidelines.Results:There were a total of 5 patients (2 males and 3 females) in family 1. The proband was an 8-year-old girl, showed syndactyly of the third and fourth fingers of the right hand with webbed fusion and distal fingernail fusion. The rest of the fingers and feet were normal. There were a total of 4 patients (all females) in family 2. The proband was a 4-year-old girl, and showed the interlocking of the third and fourth fingers on both hands and the lateral curvature of the indicator finger. Two mutations of the homeobox D13(HOXD13) gene, c. 917G>A and c. 917G>T were detected and co-segregated with the disease phenotype in two affected families. Moreover, the variant of c. 917G>T is a novel missense mutation of the HOXD13 gene. According to ACMG guidelines, c. 917G>A meets the criteria of pathogenic variation (PS1+ PS4+ PM1+ PM2+ PP3) and c. 917G>T meets the criteria of likely pathogenic variation (PM2+ PM5+ PP3+ PP4).Conclusion:The HOXD13 gene c. 917G>A and c. 917G>T mutations are identified to be responsible for hereditary synpolydactyly in these two families.
