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- Title
Molecular spectrum of inherited FVII deficiency in North India revealed a recurrent variant with a founder effect.
- Authors
Sharma, Ritika; Jamwal, Manu; Senee, Hari Kishan; Singh, Namrata; Kumar, Narender; Hans, Chander; Kler, Anita; Bansal, Deepak; Trehan, Amita; Malhotra, Pankaj; Ahluwalia, Jasmina; Das, Reena
- Abstract
Introduction: Inherited Factor VII (FVII) deficiency is commonest among the rare bleeding disorders. A small number of patients present in infancy with severe bleeding, and many may remain asymptomatic but detected before surgery/invasive procedures. Genetic testing may be helpful in predictive testing/prenatal diagnosis in severe cases. Aim: Characterisation of clinical and genotypic spectrum of patients with inherited FVII deficiency. Methods: Retro‐prospectively, 35 cases with prolonged prothrombin time and FVII activity (FVII:C) <50 IU/dl were subjected to targeted resequencing. After in‐silico analysis, variant/s were validated by Sanger sequencing in index cases and family members. Haplotype analysis was done for F7 polymorphisms. Results: Severe FVII deficiency was found in 50% of patients (FVII:C ≤1 IU/dl), and 42.9% were asymptomatic. Clinical severity assessment revealed 17% severe, 17% moderate and 22.9% patients with mild bleeds. FVII levels ranged from.3 to 38 IU/dl. Molecular analysis revealed variants in 30/35 cases, of which 17 were homozygous, 10 were compound heterozygous and 3 were heterozygous. Twelve genetic variants were identified, one promoter variant c.‐30A>C; seven missense (c.215C>G, c.244T>C, c.253G>C, c.904G>A, c.961C>T, c.1109G>T, c.1211G>A), two deletions (c.21delG, c.868_870delATC), and one each of nonsense c.634C>T and splice‐site variant c.316+1G>A. Recurrent variants c.1109G>T and c.215C>G were found in 17 and 8 cases, 12 of the former cases were homozygous. They had the same haplotype, indicating the founder effect in North Indians. Conclusion: This is the largest cohort of FVII genotyping from India, confirming heterogeneity in terms of clinical manifestations, FVII activity and zygosity of the variants with a limited genotypic phenotypic correlation.
- Subjects
INDIA; MOLECULAR spectra; HAPLOTYPES; GENETIC testing; GENETIC variation; PRENATAL diagnosis; SYMPTOMS; AGROBACTERIUM tumefaciens
- Publication
Haemophilia, 2023, Vol 29, Issue 2, p591
- ISSN
1351-8216
- Publication type
Article
- DOI
10.1111/hae.14730