Detection and characterisation of large SERPINC1 deletions in type I inherited antithrombin deficiency.
Hum Genet
; 127(1): 45-53, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19760264
Methods routinely used for investigating the molecular basis of antithrombin (AT) deficiency do not detect large SERPINC1 rearrangements. Between 2000 and 2008, 86 probands suspected of having AT-inherited type I deficiency were screened for SERPINC1 mutations in our laboratory. Mutations causally linked to the deficiency were identified by sequencing analysis in 63 probands. We present here results of multiplex ligation-dependent probe amplification (MLPA) analysis performed in 22 of the 23 remaining probands, in whom sequencing had revealed no mutation. Large deletions, present at the heterozygous state, were detected in 10 patients: whole gene deletions in 5 and partial deletions removing either exon 6 (n = 2), exons 1-2 (n = 1) or exons 5-7 (n = 2) in 5 others. Exon 6 partial deletions are a 2,769-bp deletion and a 1,892-bp deletion associated with a 10-bp insertion, both having 5' and/or 3' breakpoints located within Alu repeat elements. In addition, we identified the 5' breakpoint of a previously reported deletion of exons 1-2 within an extragenic Alu repeat. Distinct mutational mechanisms explaining these Alu sequence-related deletions are proposed. Overall, in this series, large deletions detected by MLPA explain almost half of otherwise unexplained type I AT-inherited deficiency cases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antitrombinas
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Deleção de Sequência
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Deficiência de Antitrombina III
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
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Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Hum Genet
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
Alemanha