PURA syndrome is caused by a pathogenic sequence variant in the PURA gene. The PURA gene’s cytogenetic location is at 5q31.3.
The PURA gene encodes the 322-amino acid pur-alpha protein, known as purine-rich element-binding protein A. It contains a N-terminal glycine-rich region, three Pur repeat motifs (PURI, II and III) and a C-terminal glutamine–glutamate rich domain.
This ubiquitously found multifunctional protein has been shown to be a DNA and RNA binding protein that plays a role in DNA replication, DNA transcription and mRNA translation. It is present in the brain and is integral in normal brain development. It is believed that haploinsufficiency is responsible for the phenotype.
Most cases to date have been identified by genomic sequencing. However as it is added to multi-gene panels the hope is that more cases will be identified in this way.
Almost all mutations are due to a de-novo change and inheritance is considered to be autosomal dominant. If there is no evidence of the pathogenic PURA sequence variant in the parents, then this is most likely a de-novo change. In this case, the presumed risk to further children would be low. However inheritance via parental germline mosaicism is a possibility, in these cases the reoccurrence risk would be greater. In the event of further pregnancy, genetic counselling should be offered.
Other diagnoses that may have been considered and that children may have been tested for include congenital central hypoventilation syndrome, Prader-Wili syndrome, Spinal Muscular atropy 1, Myotonic dystrophy in the newborn, Rett syndrome, Pitt-Hopkins syndrome and Angelman syndrome.
It has been noted that there is some clinical phenotype overlap with individuals who have the 5q31.3 deletion. The PURA gene is one of the genes located within the deleted region. Features include developmental delay, intellectual disability and epilepsy.