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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.
GLOSSARY
- ENMG=
- electroneuromyography;
- MAC=
- membrane attack complex;
- PNH=
- paroxysmal nocturnal hemoglobinuria
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received July 15, 2014.
- Accepted in final form December 3, 2014.
- © 2015 American Academy of Neurology
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