Molecular spectrum of inherited FVII deficiency in North India revealed a recurrent variant with a founder effect
© 2022 John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Haemophilia : the official journal of the World Federation of Hemophilia - 29(2023), 2 vom: 26. März, Seite 591-599 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sharma, Ritika [VerfasserIn] |
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| Links: |
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| Themen: |
9001-25-6 |
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| Anmerkungen: |
Date Completed 20.03.2023 Date Revised 20.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/hae.14730 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350832951 |
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| 245 | 1 | 0 | |a Molecular spectrum of inherited FVII deficiency in North India revealed a recurrent variant with a founder effect |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a AIM: Characterisation of clinical and genotypic spectrum of patients with inherited FVII deficiency | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a coagulation disorders | |
| 650 | 4 | |a founder effect | |
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| 650 | 4 | |a molecular diagnosis | |
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| 700 | 1 | |a Kumar, Narender |e verfasserin |4 aut | |
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| 700 | 1 | |a Das, Reena |e verfasserin |4 aut | |
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