We report the case of a Caucasian Spanish boy, who showed profound neonatal hypotonia, feeding difficulties, apnea, severe developmental delay, epilepsy, bilateral convergent strabismus, poor verbal language development and a large brainstem. Whole-exome sequence uncovered a novel de novo mutation in the purine-rich element binding protein A gene (PURA; NM_005859.4:c.72del:p.(Gly25AlafsTer53)) that encodes the transcriptional activator protein Pur-alpha (PURA).
Mutations in this gene have been identified in patients with PURA syndrome, a rare disorder characterized by an early hypotonia, developmental delay, severe intellectual disability with or without epilepsy, and disability in expressive language development. Although, up to 75 cases have been identified worldwide, to the best of our knowledge, this is the first patient described with a brainstem larger than normal. In conclusion, our data expand both genetic and phenotypic spectrum associated with PURA gene mutations.
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The authors thank the patient and his family for their contribution. This work was supported by the Spanish Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) (grant PI17/00487 to F.M.-A.). F.J.C.-V. was supported by fellowship from the Instituto de Investigación Hospital 12 de Octubre (i+12). M.E.R-G. was supported by a fellowship from ISCIII and ERDF (grant PI17/00487).
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