𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Spectrum of molecular defects and mutation detection rate in patients with severe hemophilia A

✍ Scribed by Nadja Bogdanova; Arseni Markoff; Hartmut Pollmann; Ulrike Nowak-Göttl; Roswith Eisert; Cornelia Wermes; Albena Todorova; Antonin Eigel; Bernd Dworniczak; Jürgen Horst

Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
168 KB
Volume
26
Category
Article
ISSN
1059-7794

No coin nor oath required. For personal study only.

✦ Synopsis

Hemophilia A is the most frequently occurring X-linked bleeding disorder, affecting one to two out of 10,000 males worldwide. Various types of mutations in the F8 gene are causative for this condition. It is well known that the most common mutation in severely affected patients is the intron 22 inversion, which accounts for about 45% of cases with F8 residual activity of less than 1%. Therefore, the aim of the present study was to determine the spectrum and distribution of mutations in the F8 gene in a large group of patients with severe hemophilia A who previously tested negative for the common intron 22 inversion. Here we report on a mutation analysis of 86 patients collected under the above-mentioned criterion. The pathogenic molecular defect was identified in all patients, and thus our detection rate was virtually 100%. Thirty-four of the identified mutations are described for the first time. The newly detected amino acid substitutions were scored for potential gross or local conformational changes and influence on molecular stability for every single F8 domain with available structures, using homology modeling.

📜 SIMILAR VOLUMES

Spectrum of molecular defects and mutati
Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A
✍ Nadja Bogdanova; Arseni Markoff; Roswith Eisert; Cornelia Wermes; Hartmut Pollma 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 English ⚖ 355 KB

## Communicated by Arupa Ganguly The amount of residual F8 (FVIII:C) determines the clinical severity of hemophilia A. Recently, we showed that the mutation detection rate in severely affected male patients (FVIII:Co1% of normal) is virtually 100% when testing for the common intron 22-/intron 1-in

Frameshift mutations with severe and mod
Frameshift mutations with severe and moderate clinical phenotypes in Thai hemophilia A patients
✍ Varaporn Akkarapatumwong; Sorasak Intorasoot; Sumalee Oranwiroon; Prapaporn Than 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 17 KB 👁 2 views

Six frameshift mutations in exon 14 of the factor VIII gene were identified in Thai hemophilia A patients. Although all these mutations created premature stop codons and expected to cause severe disease, the molecular defects and clinical severity were in discrepancy in some patients. Four mutations

Molecular genetic analysis of 40 patient
Molecular genetic analysis of 40 patients with glycogen storage disease type Ia: 100% mutation detection rate and 5 novel mutations
✍ Hans H. Seydewitz; Dietrich Matern 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 23 KB 👁 2 views

Molecular genetic analysis of 40 patients with glycogen storage disease type Ia (GSD Ia) revealed mutations on all 80 alleles and verified the diagnosis in all patients. At least 7 patients were diagnosed with GSD Ia solely on the basis of clinical findings prior to our analysis. Five mutations, Q20