Analysis of HEXB gene mutations in an infant with Sandhoff disease
10.3760/cma.j.issn.1003-9406.2019.09.019
- VernacularTitle: 一例婴儿型Sandhoff病患儿的HEXB基因突变分析
- Author:
Ruohao WU
1
;
Wenting TANG
2
;
Kunyin QIU
1
;
Yu LI
1
;
Lirong LU
3
;
Dongfang LI
1
Author Information
1. Department of Paediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
2. Department of Research and Molecular Diagnostics, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
3. Kingmed Diagnostics Center, Guangzhou, Guangdong 510330, China
- Publication Type:Clinical Trail
- Keywords:
HEXB gene;
Infantile Sandhoff disease;
Compound heterozygous mutation;
Nonsense mutation
- From:
Chinese Journal of Medical Genetics
2019;36(9):930-934
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To detect potential mutations of HEXB gene in an infant with Sandhoff disease (SD).
Methods:Genomic DNA was extracted from peripheral blood sample of the infant. All coding exons (exons 1 to 14) and splicing sites of the HEXB gene were subjected to PCR amplification and direct sequencing.PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. PubMed BLAST CD-search was performed to identify functional domains destroyed by thecandidate mutations. Impact of the mutations was analyzed with software including PolyPhen-2, Mutation Taster and SIFT. Whole-exome sequencing was carried out to identify additional mutations.
Results:The infant was found to carry compound heterozygous mutations c. 1652G>A(p.Cys551Tyr) and c. 1389C>G (p.Tyr463*) of the HEXB gene. The c. 1389C>G (p.Tyr463*) mutation may lead to destruction of two functional domains in β subunit of the Hex protein. The c. 1652G>A(p.Cys551Tyr)mutation, unreported previously, was predicted to be probably damaging by Bioinformatic analysis.
Conclusion:Compound heterozygous mutations c. 1652G>A(p.Cys551Tyr) and c. 1389C>G (p.Tyr463*) in the HEXB gene probably underlie the disease in this patient.
