Spinal motor neuron involvement in a patient with homozygous PRUNE mutation

• Published in: European journal of paediatric neurology Vol. 22; no. 3; pp. 541 - 543
• Main Authors: Iacomino, Michele, Fiorillo, Chiara, Torella, Annalaura, Severino, Mariasavina, Broda, Paolo, Romano, Catia, Falsaperla, Raffaele, Pozzolini, Giulia, Minetti, Carlo, Striano, Pasquale, Nigro, Vincenzo, Zara, Federico
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2018
• Subjects: Brain development; Brain Diseases - genetics; Carrier Proteins - genetics; Developmental Disabilities - genetics; Exome sequencing; Homozygote; Humans; Infant; Male; Motor neuron; Motor Neurons - pathology; Muscle biopsy; Muscular Atrophy, Spinal - genetics; Mutation; Nervous System Malformations - genetics; Phenotype; PRUNE; Syndrome; Motor neuron; Muscle biopsy; PRUNE; Brain development; Exome sequencing
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/j.ejpn.2017.12.005

In the last few years, whole exome sequencing (WES) allowed the identification of PRUNE mutations in patients featuring a complex neurological phenotype characterized by severe neurodevelopmental delay, microcephaly, epilepsy, optic atrophy, and brain or cerebellar atrophy. We describe an additional patient with homozygous PRUNE mutation who presented with spinal muscular atrophy phenotype, in addition to the already known brain developmental disorder. This novel feature expands the clinical consequences of PRUNE mutations and allow to converge PRUNE syndrome with previous descriptions of neurodevelopmental/neurodegenerative disorders linked to altered microtubule dynamics. •PRUNE is a member of the DHH-phosphoesterase superfamily of molecules important for cell motility.•PRUNE mutations were found in cases of severe neurodevelopmental delay, epilepsy and brain atrophy.•In neuronal cells, PRUNE exhibits microtubule polymerization and migration functions, altered by mutations of the DHH domain.•We found a PRUNE DHH mutation in a 9 months child with spinal muscular atrophy phenotype, in addition to the brain developmental disorder.•This case expands the clinical effects of PRUNE mutations converging in neurodevelopmental disorders of microtubule dynamics.