Goknur Haliloglu1, Jérome Maluenda1, Bahattin Sayinbatur1, Cedric Aumont1, Cagri Temucin1, Betul Tavil1, Mualla Cetin1, Kader K Oguz1, Ivo Gut1, Veronique Picard1, Judith Melki1, Haluk Topaloglu2. 1. From the Departments of Pediatric Neurology (G.H., B.S., H.T.), Neurology (C.T.), Pediatric Hematology (B.T., M.C.), and Radiology (K.K.O.), Hacettepe University Ankara, Turkey; Unité Mixte de Recherche (UMR)-986 (J. Maluenda, J. Melki), Inserm and University Paris Sud; Hematology Laboratory (C.A., V.P.), AP-HP, CHU Bicêtre, France; and Centro Nacional de Análisis Genómico (I.G.), Barcelona, Spain. 2. From the Departments of Pediatric Neurology (G.H., B.S., H.T.), Neurology (C.T.), Pediatric Hematology (B.T., M.C.), and Radiology (K.K.O.), Hacettepe University Ankara, Turkey; Unité Mixte de Recherche (UMR)-986 (J. Maluenda, J. Melki), Inserm and University Paris Sud; Hematology Laboratory (C.A., V.P.), AP-HP, CHU Bicêtre, France; and Centro Nacional de Análisis Genómico (I.G.), Barcelona, Spain. htopalog@hacettepe.edu.tr.
Abstract
OBJECTIVE: To identify the underlying etiology of 3 patients in a multiplex family with strokes, chronic immune-mediated peripheral neuropathy, and hemolysis. All had onset in infancy. METHODS: We performed genome-wide linkage analysis followed by whole exome sequencing (WES) in the proband, Sanger sequencing, and segregation analysis of putative mutations. In addition, we conducted flow cytometry studies to assess CD59 expression. RESULTS: In a 2-generation-3-affected family with early-onset immune-mediated axonal neuropathy, cerebrovascular event both in the anterior and posterior circulation, and chronic Coombs-negative hemolysis, we detected CD59 deleterious mutation as the underlying cause. Linkage analysis and homozygosity mapping using single nucleotide polymorphism (SNP) microarrays in the family followed by WES in one index case allowed identification of a homozygous missense mutation in the CD59 gene (c.A146T:p.Asp49Val). Sanger sequencing validated the mutation, showing cosegregation with the disease phenotype. Flow cytometry using blood cells in the 3 patients showed a lack of CD59 expression at the cell membrane compared to control and CD55 labeling. CONCLUSION: We added to the knowledge base about inherited CD59 deficiency.
OBJECTIVE: To identify the underlying etiology of 3 patients in a multiplex family with strokes, chronic immune-mediated peripheral neuropathy, and hemolysis. All had onset in infancy. METHODS: We performed genome-wide linkage analysis followed by whole exome sequencing (WES) in the proband, Sanger sequencing, and segregation analysis of putative mutations. In addition, we conducted flow cytometry studies to assess CD59 expression. RESULTS: In a 2-generation-3-affected family with early-onset immune-mediated axonal neuropathy, cerebrovascular event both in the anterior and posterior circulation, and chronic Coombs-negative hemolysis, we detected CD59 deleterious mutation as the underlying cause. Linkage analysis and homozygosity mapping using single nucleotide polymorphism (SNP) microarrays in the family followed by WES in one index case allowed identification of a homozygous missense mutation in the CD59 gene (c.A146T:p.Asp49Val). Sanger sequencing validated the mutation, showing cosegregation with the disease phenotype. Flow cytometry using blood cells in the 3 patients showed a lack of CD59 expression at the cell membrane compared to control and CD55 labeling. CONCLUSION: We added to the knowledge base about inherited CD59 deficiency.
Authors: Hani Boshra; Wioleta M Zelek; Timothy R Hughes; Santiago Rodriguez de Cordoba; B Paul Morgan Journal: J Immunol Date: 2017-11-22 Impact factor: 5.422
Authors: Morten Blaabjerg; Anne Louise Hemdrup; Lylia Drici; Klemens Ruprecht; Peter Garred; Romana Höftberger; Bjarne W Kristensen; Daniel Kondziella; Tobias Sejbaek; Soren W Hansen; Helle H Nielsen; Pia Jensen; Morten Meyer; Friedemann Paul; Hans Lassmann; Martin R Larsen; Zsolt Illes Journal: Front Immunol Date: 2018-04-23 Impact factor: 7.561