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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
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A Splice Site Mutation Associated with Congenital CD59 Deficiency
Jiani N Chai1, Abul Kalam Azad1, Kevin Kuan1
1Department of Pathology, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, 111 East 210th Street, New York, NY 10467, USA.
Hematology Reports
|June 23, 2022
Summary
Congenital CD59 deficiency, a rare genetic disorder, can now be identified by a novel splice site mutation in the CD59 gene. This discovery aids in diagnosing patients with chronic hemolysis and neurological symptoms.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Congenital CD59 deficiency is a rare autosomal recessive disorder.
- It results from CD59 gene mutations, causing deficient cell surface CD59 protein.
- Clinical features include chronic hemolysis, demyelinating neuropathy, and ischemic strokes.
Observation:
- A case study of a young boy with early-onset neuropathy and atypical hemolytic uremic syndrome is presented.
- Next-generation sequencing identified a homozygous splice site variant (c.67 + 1G > T) in intron 1 of the CD59 gene.
- This variant affects a critical splicing site, leading to significantly reduced CD59 mRNA and protein expression.
Findings:
- The identified splice site mutation is the first reported cause of congenital CD59 deficiency.
- Quantitative reverse transcription PCR confirmed a drastic reduction in CD59 mRNA levels.
- Flow cytometry demonstrated a complete absence of CD59 protein on red blood cells.
Implications:
- This finding expands the known mutational spectrum for congenital CD59 deficiency.
- Early diagnosis through genetic testing can be facilitated by identifying this specific variant.
- Understanding the molecular basis of CD59 deficiency aids in developing targeted therapies.
Keywords:
CD59atypical hemolytic uremic syndromecongenital CD59 deficiencynext-generation sequencing (NGS)splice site mutationMore Related Videos
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