DNA Sequencing Clinical Trial
Official title:
First Description of a Severe Ivermectin Neurotoxicity in a Child Carrying ABCB1 Nonsense Mutations.
The study report a unique case of severe intoxication in a child treated with oral ivermectin
to prevent scabies infection. The ABCB1 gene sequencing found the child compound heterozygote
for two nonsense mutations, one in each gene copy. The child had inherited from each parent
one of the alleles. Each mutation generate a predicted truncated protein that likely lead to
ABCB1 loss of function, and the undesirable effects observed.
The study report a unique case of severe intoxication in a child treated with oral ivermectin
to prevent scabies infection. The ABCB1 gene sequencing found the child compound heterozygote
for two nonsense mutations, one in each gene copy. The child had inherited from each parent
one of the alleles. Each mutation generate a predicted truncated protein that likely lead to
ABCB1 loss of function, and the undesirable effects observed.
While in some animals, nonsense ABCB1 mutations can lead to neurotoxicity of several
ABCB1-substrate drugs, in humans, ivermectin was considered to have an especially high margin
of safety, and nonsense mutations have never been reported before, nor has the neurotoxicity
of ivermectin apparently caused by these two mutations never been reported before.
This discovery is of critical importance for the child, since it dictates that clinicians
would need to optimize any ABCB1 substrate-based therapy in the future. More generally, such
information must be brought to the attention of clinicians' medics, and in particular
infectious disease specialists, pediatricians, and general practitioners.
It points the importance of pharmacovigilance, and the benefit of pharmacogenomic genotyping
in well-defined phenotype, still too rarely considered in clinical practice before the
implementation of a drug treatment.
This work results from a multidisciplinary approach, combining several areas of expertise in
clinical pediatrics, pharmacology, biology, and bioinformatics.
n/a
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT03971292 -
Interest of High-throughput Sequencing of RNAs for the Diagnosis of Heterogeneous Genetic Diseases
|