Characterization of genetic defects of hemophilia A in patients of Chinese origin

Journal Article · Wed Dec 01 04:00:00 EST 1993 · Genomics; (United States)

DOI:https://doi.org/10.1016/S0888-7543(11)80005-4· OSTI ID:6974461

Lin, Shu-Wha; Lin, Shu-Rung; Shen, Ming-Ching ^[1]

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1. National Taiwan Univ., Taipei (Taiwan, Province of China)

The molecular characterization of hemophilia A of Chinese origin was carried out by the polymerase chain reaction (PCR) and direct sequencing of patient's factor VIII genes. Single-strand conformation polymorphism (SSCP) and dideoxy fingerprinting (ddF) were used as screening methods to detect mutated DNAs. A total of 102 individuals from 87 different families, including 10 patients (10 families) with mild-to-moderate and 92 patients (77 families) with severe hemophilia A, were analyzed by PCR-SSCP and PCR-ddF. Of the 87 independent cases, 40 revealed a single mutation in the coding regions of their factor VIII genes. These mutations include 21 with single base changes resulting in 8 nonsense and 13 missense codons, 16 with deletion or insertion of 1-11 nucleotides, and 3 with deletion of large DNA fragments. The frequency of 8 of the identified factor VIII polymorphisms or silent mutations was also determined among Chinese. The frequencies for codons 1241, 1269, and 2223 (the numbering system follows J. Gitschier et al., 1984, Nature 312: 326-330) were found to be different from those reported for other populations. As for the 47 severe cases whose mutational events were not readily detected by PCR-SSCP and PCR-ddF, the reverse transcriptase PCR method was applied. In 24 such cases analyzed, 17 were found to be of the [open quotes]intron 22 mutations[close quotes] as described by Naylor et al. (1992, The Lancet, 342: 1066-1067), accounting for 39% of Chinese patients with hemophilia A. 31 refs., 2 figs., 6 tabs.

• OSTI ID: 6974461
• Journal Information: Genomics; (United States), Journal Name: Genomics; (United States) Vol. 18:3; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
550900 -- Pathology
59 BASIC BIOLOGICAL SCIENCES
BLOOD COAGULATION FACTORS
COAGULANTS
DETECTION
DISEASES
DNA HYBRIDIZATION
DNA SEQUENCING
DRUGS
GENE MUTATIONS
HEMATOLOGIC AGENTS
HEMIC DISEASES
HEMOPHILIA
HEREDITARY DISEASES
HYBRIDIZATION
MUTATIONS
ORGANIC COMPOUNDS
PATHOGENESIS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS