Factor VIII Gene Mutations in Korean Patients with Hemophilia A.

Choi, Young Min; Kim, Eun Joo; Lee, Mi Ran; Son, Young Soo; Choe, Jin; Hwang, Doyeong; Jun, Jong Kwan; Jee, Byung Chul; Ku, Seung Yup; Suh, Chang Suk; Kim, Seok Hyun; Kim, Jung Gu; Moon, Shin Yong

Original Article

Korean Journal of Obstetrics & Gynecology 2004;47(10):1975-1981.
Published online October 1, 2004.

Factor VIII Gene Mutations in Korean Patients with Hemophilia A.

Young Min Choi, Eun Joo Kim, Mi Ran Lee, Young Soo Son, Jin Choe, Doyeong Hwang, Jong Kwan Jun, Byung Chul Jee, Seung Yup Ku, Chang Suk Suh, Seok Hyun Kim, Jung Gu Kim, Shin Yong Moon

¹Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Korea.
²Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Korea.
³Hamchoon Women's Clinic, Korea.
⁴Korea Hemophilia Foundation Clinic, Korea.
⁵Department of Obstetrics and Gynecology, Cheongju St. Mary Hospital, Cheongju, Korea.

Abstract

OBJECTIVE
To identify mutations within the factor VIII gene in Korean patients with severe hemophilia A. DESIGN: A laboratory analysis. METHODS: We systematically sequenced the promoter, all exons and splice junctions of factor VIII gene in 23 unrelated Korean patients with severe hemophilia A. Patients with factor VIII gene inversion were excluded. RESULTS: Twelve patients (52.2%) showed a point mutation, among which 6 were nonsense mutations and the other 6 were missense mutations. A large deletion was found in 6 (26.1%) patients, a small deletion in 2 (8.7%), a small insertion in one patient. Two patients had compound mutations: one patient had two missense mutations, and the other had a missense mutation and 4 bp insertion. Ten (43.5%) out of 23 mutations found are novel. CONCLUSION: Mutations within the factor VIII gene found in Korean patients with moderate to severe hemophilia A are diverse as expected. And we have found 10 novel mutations. Our results can help understanding the molecular pathology of hemophilia A.

Key Words: Hemophila A, Mutation, Factor VIII gene