IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Identification of two novel single nucleotide variants of the complement Factor H (CFH) and Factor I (CFI) genes in a familial form of atypical hemolytic uremic syndrome (aHUS)
Autor/es:
SMITH RJH; GRELONI G; DOS SANTOS C; CASINELLI MM; KEMPFER AC; SÁNCHEZ LUCEROS A
Reunión:
Congreso; 62nd Annual Meeting of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis; 2016
Institución organizadora:
International Society on Thrombosis and Haemostasis
Resumen:
Background: Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Most aHUS cases involve sequence variations in genes encoding complement proteins.Aims: A 27-year-old woman with an episode of thrombotic microangiopathy1 month post-partum presented with severe anemia (hematocrit: 22%, hemoglobin: 7.6 g/dL), thrombocytopenia (138 000/lL), elevated LDH (654 IU/L) and deteriorating renal function (creatinine: 3.3 mg/dL); she and her available relatives were screened for mutations/polymorphisms in aHUS-associated complement genes.Methods: After extracting gDNA from whole blood (Wizard Genomic DNA Purification Kit, Promega), PCR products of coding sequences and intronic flanking regions of complement genes were sequenced by ABI PRISM 310 Genetic Analyzer (Applied Biosystems).In silico analysis for pathogenicity was completed with Polyphen2-HDIV, PhyloP/Phastcons (MutationTaster), SIFT and PANTHER. All the participants provided informed written consent. Results: The patient was diagnosed with aHUS (all ADAMTS13 parameters were normal). Comprehensive screening of aHUS-associated complement genes identified two novel single nucleotide variants:CFH c.575G>A, p.C192Y (exon 5) (NM_000186), predicted to be pathogenic by 4 of 5 available pathogenicity prediction programs; and CFI c.1189G>T, p.V397L (exon 11) (NM_000204), predicted pathogenic by 0 of 6 available pathogenicity prediction programs.