Abstract
Mutations in complement factor H (HF1) gene have been reported in non-Shiga toxin-associated and diarrhoea-negative haemolytic uraemic syndrome (D-HUS). We analysed the complete HF1 in 101 patients with HUS, in 32 with thrombotic thrombocytopenic purpura (TTP) and in 106 controls to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and non-mutation carriers and the role of HF1 polymorphisms in the predisposition to HUS. We found 17 HF1 mutations (16 heterozygous, one homozygous) in 33 HUS patients. Thirteen mutations were located in exons XXII and XXIII. No TTP patient carried HF1 mutations. The disease manifested earlier and the mortality rate was higher in mutation carriers than in non-carriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in non-mutated patients half of the grafts were functioning after 1 year. Three HF1 polymorphic variants were strongly associated with D-HUS: -257T (promoter region), 2089G (exonXIV, silent) and 2881T (963Asp, SCR16). The association was stronger in patients without HF1 mutations. Two or three disease-associated variants led to a higher risk of HUS than a single one. Analysis of available relatives of mutated patients revealed a penetrance of 50%. In 5/9 families the proband inherited the mutation from one parent and two disease-associated variants from the other, while unaffected carriers inherited the protective variants. In conclusion HF1 mutations are frequent in patients with D-HUS (24%). Common polymorphisms of HF1 may contribute to D-HUS manifestation in subjects with and without HF1 mutations.
| Original language | English |
|---|---|
| Pages (from-to) | 3385-3395 |
| Number of pages | 11 |
| Journal | Human Molecular Genetics |
| Volume | 12 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - Dec 15 2003 |
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ASJC Scopus subject areas
- Genetics
Cite this
Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome : The C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. / Caprioli, Jessica; Castelletti, Federica; Bucchioni, Sara; Bettinaglio, Paola; Bresin, Elena; Pianetti, Gaia; Gamba, Sara; Brioschi, Simona; Daina, Erica; Remuzzi, Giuseppe; Noris, Marina.
In: Human Molecular Genetics, Vol. 12, No. 24, 15.12.2003, p. 3385-3395.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome
T2 - The C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease
AU - Caprioli, Jessica
AU - Castelletti, Federica
AU - Bucchioni, Sara
AU - Bettinaglio, Paola
AU - Bresin, Elena
AU - Pianetti, Gaia
AU - Gamba, Sara
AU - Brioschi, Simona
AU - Daina, Erica
AU - Remuzzi, Giuseppe
AU - Noris, Marina
PY - 2003/12/15
Y1 - 2003/12/15
N2 - Mutations in complement factor H (HF1) gene have been reported in non-Shiga toxin-associated and diarrhoea-negative haemolytic uraemic syndrome (D-HUS). We analysed the complete HF1 in 101 patients with HUS, in 32 with thrombotic thrombocytopenic purpura (TTP) and in 106 controls to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and non-mutation carriers and the role of HF1 polymorphisms in the predisposition to HUS. We found 17 HF1 mutations (16 heterozygous, one homozygous) in 33 HUS patients. Thirteen mutations were located in exons XXII and XXIII. No TTP patient carried HF1 mutations. The disease manifested earlier and the mortality rate was higher in mutation carriers than in non-carriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in non-mutated patients half of the grafts were functioning after 1 year. Three HF1 polymorphic variants were strongly associated with D-HUS: -257T (promoter region), 2089G (exonXIV, silent) and 2881T (963Asp, SCR16). The association was stronger in patients without HF1 mutations. Two or three disease-associated variants led to a higher risk of HUS than a single one. Analysis of available relatives of mutated patients revealed a penetrance of 50%. In 5/9 families the proband inherited the mutation from one parent and two disease-associated variants from the other, while unaffected carriers inherited the protective variants. In conclusion HF1 mutations are frequent in patients with D-HUS (24%). Common polymorphisms of HF1 may contribute to D-HUS manifestation in subjects with and without HF1 mutations.
AB - Mutations in complement factor H (HF1) gene have been reported in non-Shiga toxin-associated and diarrhoea-negative haemolytic uraemic syndrome (D-HUS). We analysed the complete HF1 in 101 patients with HUS, in 32 with thrombotic thrombocytopenic purpura (TTP) and in 106 controls to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and non-mutation carriers and the role of HF1 polymorphisms in the predisposition to HUS. We found 17 HF1 mutations (16 heterozygous, one homozygous) in 33 HUS patients. Thirteen mutations were located in exons XXII and XXIII. No TTP patient carried HF1 mutations. The disease manifested earlier and the mortality rate was higher in mutation carriers than in non-carriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in non-mutated patients half of the grafts were functioning after 1 year. Three HF1 polymorphic variants were strongly associated with D-HUS: -257T (promoter region), 2089G (exonXIV, silent) and 2881T (963Asp, SCR16). The association was stronger in patients without HF1 mutations. Two or three disease-associated variants led to a higher risk of HUS than a single one. Analysis of available relatives of mutated patients revealed a penetrance of 50%. In 5/9 families the proband inherited the mutation from one parent and two disease-associated variants from the other, while unaffected carriers inherited the protective variants. In conclusion HF1 mutations are frequent in patients with D-HUS (24%). Common polymorphisms of HF1 may contribute to D-HUS manifestation in subjects with and without HF1 mutations.
UR - http://www.scopus.com/inward/record.url?scp=0242601270&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242601270&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddg363
DO - 10.1093/hmg/ddg363
M3 - Article
C2 - 14583443
AN - SCOPUS:0242601270
VL - 12
SP - 3385
EP - 3395
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 24
ER -