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. 2023 May;76(5):339-344.
doi: 10.1136/jclinpath-2021-207703. Epub 2021 Nov 29.

Determining common variants in patients with haemophilia A in South Vietnam and screening female carriers in their family members

Bang Suong Thi Nguyen  1   2 , Xuan Thao Thi Le  1   2 , Nghia Huynh  1 , Huy Huu Nguyen  2 , Cong-Minh Truong Nguyen  1   2 , Bac Hoang Nguyen  3   2
Affiliations

Determining common variants in patients with haemophilia A in South Vietnam and screening female carriers in their family members

Bang Suong Thi Nguyen et al. J Clin Pathol. 2023 May.

Abstract

Aims: The aim of this study was to determine common variants in F8, including intron 22 inversion (Inv22), intron 1 inversion (Inv1) and point mutations, the transmission of these variants between patients with haemophilia A (HA) and their family members.

Methods: Genetic analysis was conducted in 71 patients who were clinically diagnosed with HA and 152 related female members in South Vietnam by a combination of inversion PCR (I-PCR), multiplex PCR and direct sequencing.

Results: Variants in F8, including Inv22, point mutations (with 37 genotypes) and two novel variants, occupied 60 patients with HA. Among severe patients, the rate of Inv22 was 44%. Missense was the common point mutation of over 50% in patients with moderate HA and mild HA. Inv1 was absent in all patients. F8 variants were also found in 119 female carriers (FCs) (78.3%) from families related to patients with HA. There were 56 mothers (93.3%) carrying F8 variants and passing the same variants to their sons.

Conclusions: These findings were the first to provide important information about the presence of Inv22 and point mutation in Vietnamese patients with HA, the mothers and their female family members. It demonstrated that genetic diagnosis and counselling for HA carriers were essential factors for future improvements in comprehensive and equitable healthcare polices for patients with HA and FCs in Vietnam.

Keywords: biochemistry; genetics; hemophilia A.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Procedure of identifying variants in F8 in patients with HA and female members of haemophiliac family. HA, haemophilia A.
Figure 2
Figure 2
Summary report of identified variants in F8 in patients with HA and heterozygous carriers. HA, haemophilia A.
Figure 3
Figure 3
Sequencing results of new variants in F8. (A) Hem23 patient carried a novel variant that a single-nucleotide substitution from T to A at position c.2025 changes TAT trio encode tyrosine to TAA. It was caused by stopping transcript at exon 13 encode of A2 region. (B) Hem43 patient carried a new point mutation at exon 14 (c.4450A>G) that codon AGT changed to GGT, expression p.Ser1484Gly. (C) A frameshift variant in Hem65, c.4976delC on exon 14 of F8 gene. (D) Variant in Hem65’s mother.
Figure 4
Figure 4
PCR result of intro 22 inversion variant. M, PCR marker; 1, patient no Inv22 variant (band at 487 bp); 2, Hem17 patient with Inv22 (band at 559 bp); 3, Hem17’s mother; 4, Hem17’s first aunt; 5, Hem17’s second aunt; 6, first aunt’s daughter.
See this image and copyright information in PMC

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