Direct and indirect gene diagnosis of hemophilia A pedigrees in the Chinese population

  • Authors:
    • Ying Cao
    • Luxi Shen
    • Rong Huang
    • Lingcong Yang
    • Zhuanyun Du
    • Hua Ma
    • Tianjin Zheng
    • Haihua Gu
    • Hongzhi Li
  • View Affiliations

  • Published online on: August 17, 2017     https://doi.org/10.3892/mmr.2017.7263
  • Pages: 5722-5728
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Abstract

Hemophilia A (HA) is an X‑linked recessive hereditary disorder caused by defects in the coagulation factor VIII (FVIII) gene. In order to diagnose patients with presymptomatic HA and carriers, the present study conducted direct gene diagnosis for the common abnormalities in FVIII and subsequently performed indirect gene diagnosis for the other abnormalities in FVIII for Chinese HA pedigrees. Direct gene diagnosis was performed in 10 HA pedigrees using inverse shifting‑polymerase chain reaction to detect intron 22 inversion (inv22), intron 22 deletion, intron 22 duplication and inv1 of FVIII. Pedigrees with no detected mutations were further analyzed using indirect genetic diagnosis (haplotype linkage analysis), where the genetic markers of FVIII included one variable number of tandem repeat, seven short tandem repeats and three restriction fragment length polymorphisms. The results of three pedigrees were taken as examples. Pedigree 1 underwent direct gene diagnosis, which demonstrated that the proband was inv22 distal pattern hemophiliac and the mother was an inv22 distal pattern carrier. The other two pedigrees were subjected to indirect gene diagnosis. In pedigree 2, the detection of DXS52, 13(CA) n, DXS9901(GT) n, intron (int)18, int19 and int22 confirmed the proband's baby brother was normal, the proband's maternal aunt was a carrier and her baby son was normal. Detection of DXS9901(GT)n, int18, int19 and int22 in pedigree 3 demonstrated that the proband's maternal grandmother was not a carrier. As the maternal grandfather was not affected by the disease, it was deduced that a mutation of FVIII occurred in the proband's mother. The combination of direct and indirect gene diagnoses provides reliable evidence for the use of genetic counseling in HA pedigrees, particularly for screening presymptomatic males and female carriers with normal offspring.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Cao Y, Shen L, Huang R, Yang L, Du Z, Ma H, Zheng T, Gu H and Li H: Direct and indirect gene diagnosis of hemophilia A pedigrees in the Chinese population. Mol Med Rep 16: 5722-5728, 2017.
APA
Cao, Y., Shen, L., Huang, R., Yang, L., Du, Z., Ma, H. ... Li, H. (2017). Direct and indirect gene diagnosis of hemophilia A pedigrees in the Chinese population. Molecular Medicine Reports, 16, 5722-5728. https://doi.org/10.3892/mmr.2017.7263
MLA
Cao, Y., Shen, L., Huang, R., Yang, L., Du, Z., Ma, H., Zheng, T., Gu, H., Li, H."Direct and indirect gene diagnosis of hemophilia A pedigrees in the Chinese population". Molecular Medicine Reports 16.4 (2017): 5722-5728.
Chicago
Cao, Y., Shen, L., Huang, R., Yang, L., Du, Z., Ma, H., Zheng, T., Gu, H., Li, H."Direct and indirect gene diagnosis of hemophilia A pedigrees in the Chinese population". Molecular Medicine Reports 16, no. 4 (2017): 5722-5728. https://doi.org/10.3892/mmr.2017.7263