Chromosomal rearrangement—A rare cause of complement factor I associated atypical haemolytic uraemic syndrome

• Published in: Immunobiology (1979) Vol. 221; no. 10; pp. 1124 - 1130
• Main Authors: Gleeson, Patrick J, Wilson, Valerie, Cox, Thomas E, Sharma, Seema D, Smith-Jackson, Kate, Strain, Lisa, Lappin, David, McHale, Teresa, Kavanagh, David, Goodship, Timothy H.J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.10.2016
• Subjects: Adult; Advanced Basic Science; Alleles; Allergy and Immunology; Atypical haemolytic uraemic syndrome; Atypical Hemolytic Uremic Syndrome - blood; Atypical Hemolytic Uremic Syndrome - diagnosis; Atypical Hemolytic Uremic Syndrome - genetics; Atypical Hemolytic Uremic Syndrome - immunology; Chromosomal rearrangement; Chromosome Breakpoints; Complement; Complement Factor I - genetics; Complement Factor I - immunology; Complement System Proteins - genetics; DNA Mutational Analysis; Factor I; Genetic Predisposition to Disease; Genetic variants; Genotype; Humans; Male; Mutation; Polymorphism, Single Nucleotide; Translocation, Genetic; Atypical haemolytic uraemic syndrome; Complement; Chromosomal rearrangement; Genetic variants; Factor I
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2016.05.002

Abstract 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 875,324 bp 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.