Genetic cause found for rare congenital disease

Study: Exome sequencing identifies NBEAL2 as the causative gene for grey platelet syndrome.
By: Albers C.A. et al. (20 authors total)
In: Nature Genetics

What this study set out to do:

The study authors set out to identify genes responsible for gray platelet syndrome.

How they went about it:

The exomes of four unrelated individuals with gray platelet syndrome were sequenced. Due to the autosomal recessive nature in which this rare condition is inherited, the researchers looked for at least two novel mutations per individual in the same gene.

Outcome:

All four of the sequenced individuals had at least two novel mutations, which were predicted to have functional consequences, in the Neurobeachin-like 2 gene (NBEAL2). This gene is located on chromosome 3p21 – a region previously established as linked to gray platelet syndrome. Additional functional work was conducted in the Zebrafish which support the involvement of the NBEAL2 protein in disease aetiology.

Conclusion:

The study authors identified novel mutations in NBEAL2, a gene involved in the formation of α-granules and that “this discovery may lead to the development of safer antiplatelet drugs for use in the treatment of individuals with heart attack and stroke”.
Our view:

This study along with two others also published in the journal Nature Genetics by Kahr et al. and Gunay-Aygun et al. highlight the growing use of modern genomic technologies in identifying genes involved in rare conditions such as gray platelet syndrome. No mutations in this gene were identified in over 600 individuals from the 1000 Genomes Database and a further 100 ethnically matched controls raising the possibility of a diagnostic genetic test.

However, no correlations were made between genotype and phenotype other than to say that individuals with homozygous or compound heterozygous mutations in the NBEAL2 gene had gray platelet syndrome. Until such links are made, the test would not provide prognostic information, potentially limiting utility.

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