Chromosomal rearrangement-A rare cause of complement factor I associated atypical haemolytic uraemic syndrome.
Chromosomal rearrangements affecting the genes encoding complement factor H and the factor H related proteins have been described in aHUS patients. To date such disorders have not been described in other aHUS associated genes. We describe here a heterozygous 875,324bp deletion encompassing the gene (CFI) encoding complement factor I and ten other genes. The index case presented with aHUS and did not recover renal function. No abnormalities were detected on Sanger sequencing of CFI but a low factor I level led to a multiplex ligation-dependent probe amplification assay being undertaken. This showed a complete heterozygous deletion of CFI. The extent of the deletion and the breakpoint was defined. In the Newcastle aHUS cohort we have identified and report here 32 different CFI variants in 56 patients but to date this is the only deletion that we have identified. This finding although rare does suggest that screening for chromosomal rearrangements affecting CFI should be undertaken in all aHUS patients particularly if the factor I level is unexplainably low.
Departments of Nephrology and Histopathology, University Hospital Galway, Galway, Ireland.
Patrick J
PJ
Gleeson
Northern Molecular Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Valerie
V
Wilson
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Thomas E
TE
Cox
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Seema D
SD
Sharma
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Kate
K
Smith-Jackson
Northern Molecular Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Lisa
L
Strain
Departments of Nephrology and Histopathology, University Hospital Galway, Galway, Ireland.
David
D
Lappin
Departments of Nephrology and Histopathology, University Hospital Galway, Galway, Ireland.
Teresa
T
McHale
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
David
D
Kavanagh
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address: t.h.j.goodship@ncl.ac.uk.
Timothy H J
TH
Goodship
D000328:Adult; D000483:Alleles; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D056905:Chromosome Breakpoints; D017244:Complement Factor I / Q000235:genetics* / Q000276:immunology*; D003165:Complement System Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D014178:Translocation, Genetic
D003165:Complement System Proteins; D017244:Complement Factor I
Atypical haemolytic uraemic syndrome; Chromosomal rearrangement; Complement; Factor I; Genetic variants