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Published on: August 15, 2019
Biallelic potential disease-causing missense variants in TAF1A in two siblings with infantile restrictive
Nan Jiang1, Wenyuan Xu2, Aliaa Abdelhakim3
1Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, United States; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Insights
TAF1A gene variants are linked to a rare form of pediatric cardiomyopathy. This study identifies new cases, strengthening the evidence for TAF1A
Area of Science:
- Genetics and Molecular Biology
- Cardiology
- Pediatrics
Background:
- TAF1A, a TATA-box binding protein crucial for ribosomal RNA synthesis, has been implicated as a candidate gene for pediatric cardiomyopathy.
- Previous reports identified biallelic TAF1A variants in two families with pediatric cardiomyopathy, suggesting a potential genetic link.
Observation:
- A third family presented with two siblings exhibiting infantile restrictive cardiomyopathy, congenital leukoencephalopathy, ventriculomegaly, and feeding intolerance.
- Both siblings carried distinct biallelic missense variants in the TAF1A gene: c.1021G>A (p.(Gly341Arg)) and c.781A>C (p.(Thr261Pro)).
- Clinical manifestations included hemophagocytic lymphohistiocytosis (HLH) in one sibling and cardiac transplantation in the other, highlighting disease severity.
Findings:
- This study provides further evidence supporting the association between TAF1A gene variants and autosomal recessive pediatric cardiomyopathy.
- The identified variants expand the spectrum of TAF1A mutations linked to this cardiac condition.
Implications:
- These findings underscore the importance of genetic testing for TAF1A in diagnosing pediatric cardiomyopathy, especially with co-occurring neurological and immunological features.
- Further research into TAF1A's role in cardiac development and function may reveal therapeutic targets for related cardiomyopathies.
Abstract:
TAF1A, a gene encoding a TATA-box binding protein involved in ribosomal RNA synthesis, is a candidate gene for pediatric cardiomyopathy as biallelic TAF1A variants were reported in two families with affected individuals. Here, we report a third family with two siblings who presented with infantile restrictive cardiomyopathy and carried biallelic missense variants in TAF1A (NM_001201536.1:c.1021G>A p.(Gly341Arg) and c.781A>C p.(Thr261Pro)). Additional shared clinical features in the siblings included feeding intolerance, congenital leukoencephalopathy, ventriculomegaly and concern for primary immunodeficiency. The first-born sibling passed away at 6 months of age due to complications of hemophagocytic lymphohistiocytosis (HLH) whereas the second sibling underwent cardiac transplantation at 1 year of age and is currently well. We compare the clinical and molecular features of all the TAF1A associated cardiomyopathy cases. Our study adds evidence for the gene-disease association of TAF1A with autosomal recessive pediatric cardiomyopathy.
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