This blog is set up to find other 'cases' with RPS23 Gene mutations.
Mutations on ribosomal protein genes are very rare. Information is difficult to find and physicians are not familiar with it. Over the years I have read a lot about it and contacted most of the leading researchers in the field.
Friday, March 10, 2017
Yale press release today:
Yale team helps father discover source of sons disability
I got confirmation of a second child with 'overlapping features' in the Netherlands with a RPS23 de novo mutation.
I found a contact through GeneMatcher.org that lead to the University hospital where they found this mutation.
We got some information on the 'overlapping features' but we really want to know the specifics of the mutation. According to the clinical genetics department of that University hospital the parents of the child don't want to be involved in further research.
If that's the case I respect that of course!
But for our further research, especially on autism (neurodevelopment), a second case is very important.
It is great already that we found this match and that we were able to compare the 'overlapping features'.
The autism researchers I reached out to would like to know the specifics of the mutation.
They don't need the identity, just the description of the mutation like this:
Vincent's mutation is a heterozygous missense mutation:
RESULT AND MOLECULAR INTERPRETATION
By using exome sequencing technique, a de novo missense mutation was detected:
The mutation nomenclature is according to the HGVS guidelines (www.HGVS.org).
The change in RPS23 concerns a substitution of a highly conserved aminoacid in the ribosomal protein S12/S23 domain.
Mutations in RPS23 are currently not known to be involved in genetic disease.
TECHNICAL DESCRIPTION of the TEST
Exome sequencing was performed by a SOLiDv4 machine of Life TechnologiesTM, after enrichment of the exome by the Agilent SureSelectXT Human All Exon 50Mb Kit. Data were analysed by using the BioScopeTM software. The analysis is focused on the identification of de novo variants. The de novovariants are identified by comparing the exome data of the patient with the exome data of both parents. The variant in RPS23 was confirmed by Sanger sequencing.
I think that we are looking at 'the tip of an iceberg' here and many other RPS23 mutations will emerge in the future. Exome sequencing is becoming common practice in the near future.
It would be very good for all those patients and their parents that they can be informed on this.
I am currently planning to set up a foundation to finance further research. This further research is very important to understand what really is going on on a molecular level, in the cells and how the mutation is causative to these features.
It would be wonderful if we could have the (anonymous) mutation data.
There is no scientific evidence for any treatment of this specific mutation.
Nevertheless some alleviation of symptoms caused by other RP mutations is seen by L-Leucine and Nucleosides (Purines and Pyrimidines) supplementation.
Both the clinical trial and the mentioned study are done for DBA research. The treatments are focussed on red blood cell production. DBA(Diamond Blackfan Anemia) is the most known RP mutations related disease. This specific RPS23 mutation seems not to cause DBA.
However in the studies on L-Leucine and Nucleosides it is reported that other symptoms (like reduced cell-growth and anamolies) are partially rescued as well.
That's why we use these supplements together with vitamins, minerals, other amino acids and a normal healthy food pattern.
Of course this is no scientifically based treatment, everybody should first consult his own physician.
The anemia in DBA is treated with steroids, blood transfusions, and in some patients with stem cell transplantation.
Promising research is ongoing to develop gene therapy.