Journal article
Complement Factor H Gene Mutation Associated with Autosomal Recessive Atypical Hemolytic Uremic Syndrome
American journal of human genetics, Vol.65(6), pp.1538-1546
1999
DOI: 10.1086/302673
PMCID: PMC1288364
PMID: 10577907
Abstract
Atypical hemolytic uremic syndrome (HUS) presents with the clinical features of hypertension, microangiopathic hemolytic anemia, and acute renal failure. Both dominant and recessive modes of inheritance have been reported. This study describes the genetic and functional analysis of a large Bedouin kindred with autosomal recessive HUS. The kindred consists of several related nuclear families in which all parent unions of affected children are consanguineous. A previous report demonstrated that a dominant form of HUS maps to chromosome 1q and that complement factor H (CFH), a regulatory component of the complement system, lies within the region and is involved in the dominant disorder. Early-onset and persistent hypocomplementemia in this Bedouin kindred prompted us to evaluate the CFH gene. Linkage analysis was performed, demonstrating linkage between the disorder and the markers near the CFH gene. Mutation analysis of the CFH coding region revealed a single missense mutation. Functional analyses demonstrate that the mutant CFH is properly expressed and synthesized but that it is not transported normally from the cell. This is the first study reporting that a recessive, atypical, early-onset, and relapsing HUS is associated with the CFH protein and that a CFH mutation affects intracellular trafficking and secretion.
Details
- Title: Subtitle
- Complement Factor H Gene Mutation Associated with Autosomal Recessive Atypical Hemolytic Uremic Syndrome
- Creators
- Lihua Ying - Howard Hughes Medical Institute, University of Iowa, Iowa City, IowaYitzhak Katz - Assaf Harofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Tel AvivMenachem Schlesinger - Barzilai Medical Centers, Ben Gurion University of the Negev, Beer Sheva, IsraelRivka Carmi - Departments of Pediatrics, Soroka, IsraelHanna Shalev - Departments of Pediatrics, Soroka, IsraelNeena Haider - Department of Pediatrics, University of Iowa, Iowa City, IowaGretel Beck - Department of Pediatrics, University of Iowa, Iowa City, IowaVal C Sheffield - Howard Hughes Medical Institute, University of Iowa, Iowa City, IowaDaniel Landau - Departments of Pediatrics, Soroka, Israel
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.65(6), pp.1538-1546
- Publisher
- Elsevier Inc
- DOI
- 10.1086/302673
- PMID
- 10577907
- PMCID
- PMC1288364
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 1999
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065492102771
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