血液疾病与输血杂志

抽象的

A Novel Missense Mutation of F 9 Gene in Hemophilia B Patients

Lam Kah Yuen, Zubaidah Zakaria, Yuslina Mat Yusoff, Ezalia Esa, Faridah Md Afandi and Faraizah Dato Abd Karim

Background: Hemophilia B is an X-linked recessive disorder caused by mutations in the coding sequence of F9 gene, leading to dysfunctional Factor IX (FIX) protein.

Objectives: This study is to identify novel and recurrent mutations in hemophilia B patients.

Method and Materials: In this study, 9 hemophilia B patients were screened on 8 exons using polymerase chain reaction (PCR) and direct sequencing.

Results: We identified 6 point mutations, including 4 missense mutations and 2 nonsense mutations. One of the six point mutations is a novel mutation (NM_000133.3:c.230T>G) which has not been reported previously in hemophilia B database. Single nucleotide transversion of Thymine to Guanine occurs at nucleotide position 230, leading to amino acids substitution from Valine to Glycine at codon 77 in Gla domain. This amino acid substitution affects the protein structure and function in the Gla domain of FIX protein. Seven prediction tools were shown highly consistent result in predicting this novel mutation.

Conclusion: In this study, all point mutations were found in the coding sequence especially exon 2, exon 5 and exon 8 and distributed among Gla domain, EGF2 domain and SP domains. Novel mutation c.230T>G occurred at exon 2 of F9 gene which has damaging impact to decrease the stability of protein structure and dysfunction in Gla domain of FIX protein.