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. 2017 Sep 24;18(10):2049.
doi: 10.3390/ijms18102049.

E-Learning for Rare Diseases: An Example Using Fabry Disease

Chiara Cimmaruta  1 , Ludovica Liguori  2   3 , Maria Monticelli  4 , Giuseppina Andreotti  5 , Valentina Citro  6
Affiliations

E-Learning for Rare Diseases: An Example Using Fabry Disease

Chiara Cimmaruta et al. Int J Mol Sci. .

Abstract

Background: Rare diseases represent a challenge for physicians because patients are rarely seen, and they can manifest with symptoms similar to those of common diseases. In this work, genetic confirmation of diagnosis is derived from DNA sequencing. We present a tutorial for the molecular analysis of a rare disease using Fabry disease as an example.

Methods: An exonic sequence derived from a hypothetical male patient was matched against human reference data using a genome browser. The missense mutation was identified by running BlastX, and information on the affected protein was retrieved from the database UniProt. The pathogenic nature of the mutation was assessed with PolyPhen-2. Disease-specific databases were used to assess whether the missense mutation led to a severe phenotype, and whether pharmacological therapy was an option.

Results: An inexpensive bioinformatics approach is presented to get the reader acquainted with the diagnosis of Fabry disease. The reader is introduced to the field of pharmacological chaperones, a therapeutic approach that can be applied only to certain Fabry genotypes.

Conclusion: The principle underlying the analysis of exome sequencing can be explained in simple terms using web applications and databases which facilitate diagnosis and therapeutic choices.

Keywords: bioinformatics education; bioinformatics tools; laboratory guide; pharmacological chaperone; rare disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Alignment of the patient’s sequence with the reference genome using BLAT. The transition observed in the GLA gene is indicated by an asterisk.
Figure 2
Figure 2
Alignment of the patient’s sequence with the wild-type protein sequence using BLAST. A missense mutation in α-galactosidase A (AGAL) was identified (*). The sequence ID is also highlighted (**).
Figure 3
Figure 3
PolyPhen-2 graphical output.
Figure 4
Figure 4
Output of fabry-database.org.
Figure 5
Figure 5
Output of Fabry_CEP.
Figure 6
Figure 6
DNA analysis by using BLAT in the UCSC Genome Browser. (A) starting BLAT; (B) input data; and (C) list of significant hits.
Figure 7
Figure 7
DNA analysis by using BlastX.
Figure 8
Figure 8
UniProt analysis. (A) input data. (B) a selection of the output, a list of natural variants of AGAL (partial view).
Figure 9
Figure 9
PolyPhen-2 analysis. (A) input data and (B) result status.
See this image and copyright information in PMC

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