Analysis of HEXB gene mutations in an infant with Sandhoff disease.
10.3760/cma.j.issn.1003-9406.2019.09.019
- Author:
Ruohao WU
1
;
Wenting TANG
;
Kunyin QIU
;
Yu LI
;
Lirong LU
;
Dongfang LI
Author Information
1. Department of Paediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. ldf201310@163.com.
- Publication Type:Journal Article
- MeSH:
DNA Mutational Analysis;
Exons;
Heterozygote;
Humans;
Infant;
Mutation;
Polymerase Chain Reaction;
Sandhoff Disease;
genetics;
beta-Hexosaminidase beta Chain;
genetics
- 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.
