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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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Association of PRPS1 Mutations with Disease Phenotypes
Rahul Mittal1, Kunal Patel1, Jeenu Mittal1
1Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Disease Markers
|June 20, 2015
Summary
Mutations in the PRPS1 gene cause a range of disorders. S-adenosylmethionine (SAM) supplementation shows promise for treating PRPS1 deficiency syndromes like Arts syndrome.
Area of Science:
- Biochemistry
- Genetics
- Human Diseases
Background:
- Phosphoribosylpyrophosphate synthetase 1 (PRPS1) encodes the PRS-I enzyme, crucial for nucleotide synthesis.
- PRPS1 gene mutations are linked to various human diseases, with recent discoveries expanding the known phenotypes.
- Dysregulation of PRPS1 activity, either overexpression or deficiency, leads to distinct clinical manifestations.
Purpose of the Study:
- To review current literature on PRPS1-related syndromes.
- To summarize the spectrum of diseases associated with PRPS1 mutations.
- To explore potential therapeutic interventions for PRPS1-related disorders.
Main Methods:
- Literature review of PRPS1-related syndromes and their phenotypes.
- Analysis of the relationship between PRPS1 activity levels and disease presentation.
- Evaluation of current and potential treatment strategies.
Main Results:
- PRPS1 overexpression causes PRS-I superactivity, leading to purine overproduction and symptoms like uric acid overproduction, hypotonia, ataxia, neurodevelopmental abnormalities, and hearing impairment.
- PRPS1 deficiency results in X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome, with severity correlating to residual enzyme activity.
- Mild deficiency (DFNX-2) causes progressive hearing loss; moderate (CMTX5) and severe (Arts syndrome) deficiencies involve neuropathy, hearing loss, and central nervous system impairment.
Conclusions:
- S-adenosylmethionine (SAM) supplementation has shown efficacy in improving the condition of patients with Arts syndrome.
- This suggests that purine replacement therapy can alleviate symptoms in PRPS1 deficient patients.
- SAM supplementation offers a potential therapeutic avenue for a spectrum of PRPS1-related disorders.
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