Factors determining penetrance in familial atypical haemolytic uraemic syndrome

2.50
Hdl Handle:
http://hdl.handle.net/11287/593804
Title:
Factors determining penetrance in familial atypical haemolytic uraemic syndrome
Authors:
Sansbury, Francis H.; Cordell, H. J.; Bingham, Coralie; Bromilow, Gilly; Nicholls, Anthony; Powell, Roy ( 0000-0002-4959-5717 ) ; Shields, Beverley M; Smyth, Lucy; Warwicker, P.; Strain, L.; Wilson, V.; Goodship, J. A.; Goodship, T. H.; Turnpenny, Peter D.
Abstract:
BACKGROUND: Inherited abnormalities of complement are found in approximately 60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643C>G; p. Arg1215Gly) in whom a common lineage is probable. 25 individuals have been affected with aHUS with three peaks of incidence-early childhood (n=6), early adulthood (n=11) and late adulthood (n=8). Eighteen individuals who have not developed aHUS carry the mutation. METHODS: We estimated penetrance at the ages of 4, 27, 60 and 70 years as both a binary and a survival trait using MLINK and Mendel. We genotyped susceptibility factors in CFH, CD46 and CFHR1 in affected and unaffected carriers. RESULTS AND CONCLUSIONS: We found that the estimates of penetrance at the age of 4 years ranged from <0.01 to 0.10, at the age of 27 years from 0.16 to 0.29, at the age of 60 years from 0.39 to 0.51 and at the age of 70 years from 0.44 to 0.64. We found that the CFH haplotype on the allele not carrying the CFH mutation had a significant effect on disease penetrance. In this family, we did not find that the CD46 haplotypes had a significant effect on penetrance.
Citation:
J Med Genet. 2014 Nov;51(11):756-64.
Publisher:
BMJ
Journal:
Journal of medical genetics
Issue Date:
1-Nov-2014
URI:
http://hdl.handle.net/11287/593804
DOI:
10.1136/jmedgenet-2014-102498
PubMed ID:
25261570
Additional Links:
http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=25261570
Note:
RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1468-6244
Appears in Collections:
2014 RD&E publications; Clinical Genetics (Peninsula Genetics); Research & Development staff

Full metadata record

DC FieldValue Language
dc.contributor.authorSansbury, Francis H.en
dc.contributor.authorCordell, H. J.en
dc.contributor.authorBingham, Coralieen
dc.contributor.authorBromilow, Gillyen
dc.contributor.authorNicholls, Anthonyen
dc.contributor.authorPowell, Royen
dc.contributor.authorShields, Beverley Men
dc.contributor.authorSmyth, Lucyen
dc.contributor.authorWarwicker, P.en
dc.contributor.authorStrain, L.en
dc.contributor.authorWilson, V.en
dc.contributor.authorGoodship, J. A.en
dc.contributor.authorGoodship, T. H.en
dc.contributor.authorTurnpenny, Peter D.en
dc.date.accessioned2016-01-19T12:35:07Zen
dc.date.available2016-01-19T12:35:07Zen
dc.date.issued2014-11-01en
dc.identifier.citationJ Med Genet. 2014 Nov;51(11):756-64.en
dc.identifier.issn1468-6244en
dc.identifier.pmid25261570en
dc.identifier.doi10.1136/jmedgenet-2014-102498en
dc.identifier.urihttp://hdl.handle.net/11287/593804en
dc.description.abstractBACKGROUND: Inherited abnormalities of complement are found in approximately 60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643C>G; p. Arg1215Gly) in whom a common lineage is probable. 25 individuals have been affected with aHUS with three peaks of incidence-early childhood (n=6), early adulthood (n=11) and late adulthood (n=8). Eighteen individuals who have not developed aHUS carry the mutation. METHODS: We estimated penetrance at the ages of 4, 27, 60 and 70 years as both a binary and a survival trait using MLINK and Mendel. We genotyped susceptibility factors in CFH, CD46 and CFHR1 in affected and unaffected carriers. RESULTS AND CONCLUSIONS: We found that the estimates of penetrance at the age of 4 years ranged from <0.01 to 0.10, at the age of 27 years from 0.16 to 0.29, at the age of 60 years from 0.39 to 0.51 and at the age of 70 years from 0.44 to 0.64. We found that the CFH haplotype on the allele not carrying the CFH mutation had a significant effect on disease penetrance. In this family, we did not find that the CD46 haplotypes had a significant effect on penetrance.en
dc.language.isoengen
dc.publisherBMJen
dc.relation.urlhttp://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=25261570en
dc.titleFactors determining penetrance in familial atypical haemolytic uraemic syndromeen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalJournal of medical geneticsen
dc.description.noteRD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.en

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