Mutational analysis of exon 8 and exon 14 of ATP7B gene in Bangladeshi children with Wilson disease.
ATP 7B gene
Amplicon
Bangladeshi children
Exon 14
Exon 8
Hot spot
Novel mutation
Phenotype
Wilson disease
Journal
Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology
ISSN: 0975-0711
Titre abrégé: Indian J Gastroenterol
Pays: India
ID NLM: 8409436
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
14
07
2021
accepted:
25
06
2022
pubmed:
30
10
2022
medline:
6
12
2022
entrez:
29
10
2022
Statut:
ppublish
Résumé
BACKGROUND : Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the Adenosine Triphosphate 7B (ATP7B) gene. The spectrum of ATP7B mutation varies in different populations. The objective of this study was to identify the mutation in exon 8 and exon 14 of ATP7B gene in Bangladeshi children clinically diagnosed as WD. We also aimed to explore the phenotypic presentation. It was a cross sectional observational study. The study was conducted at the Department of Paediatric Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to June 2018. A total of 37 patients diagnosed with WD were enrolled for the study. Venous blood (about 3 mL) was drawn aseptically from each patient into tube containing ethyline diamine tetraacetic acid (EDTA) and preserved at -30°C for long-term preservation. The peripheral blood leukocytes of the patients and genomic DNAs were extracted. Exons 14 and 8 of ATP7B and their associated splice-site junctions were amplified by the polymerase chain reaction (PCR). The size and quantity of PCR products were verified by electrophoresis in 1.5% (w/v) agarose gel. 74 (37 × 2) PCR products were sent for Sanger Sequencing. The sequences were analyzed by Chromas version 2.6.6 software and the nucleotide blast was done by National Center for Biotechnology Information (NCBI) nucleoblast. Finally, the sequences were analyzed using AB Applied Bio systems and were matched with the reference sequences using MEGA software. In this study, a single novel homozygous mutation pLeu.1071Val in the exon 14 was found in every (100%) studied child clinically diagnosed with WD. Heterozygous mutation p.Gly1061Glu in exon14 was also found in 6 patients (11%) with WD, which is one of the common mutations in this disease. In exon 8, p.Arg778Leu mutation was detected in one patient (2.7%), which is common in the Chinese and the South Asian populations and was heterozygous. Two novel heterozygous missense mutations p.K785R (2.7%) and p.S744F (2.7%) were also found in two other children in the exon 8. We found three novel mutations in Bangladeshi children with WD, one of which may be tagged as founder mutation for Bangladeshi population. This finding indicates the necessity to study the mutation profiles of the whole ATP7B gene in our population for risk prediction. A further large-scale study will help in the development of a Mutational Data Base of Bangladeshi population with WD.
Identifiants
pubmed: 36308701
doi: 10.1007/s12664-022-01276-x
pii: 10.1007/s12664-022-01276-x
doi:
Substances chimiques
Adenosine Triphosphatases
EC 3.6.1.-
Adenosine Triphosphate
8L70Q75FXE
ATP7B protein, human
EC 7.2.2.8
Cation Transport Proteins
0
Copper-Transporting ATPases
EC 7.2.2.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
456-464Subventions
Organisme : bsmmu,ugc-banbladesh
ID : BSMMU/2017/2618(08)
Informations de copyright
© 2022. Indian Society of Gastroenterology.
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