Derya OKUR, Hülya Sevcan DAİMAGÜLER, Ayça Ersen DANYELİ, Hasan TEKGÜL, Haicui WANG, Gilbert WUNDERLİCH, Sebahattin ÇIRAK, Uluç YİŞ

Bi-allelic mutations in PRUNE lead to neurodegeneration with spinal motor neuron involvement and hyperCKaemia

We aimed to systematically investigate the neuromuscular involvement ofindividuals with PRUNE mutations who may have a major spinal motor neuroninvolvement as part of the PRUNE-associated neurodegenerative phenotype.The complex neurological phenotypes associated with Prune mutationsinclude microcephaly with brain abnormalities, spasticity, seizures, severedevelopmental delay and developmental regression. We used whole exomesequencing to identify the mutation and electrophysiological and musclebiopsy studies to evaluate the signs of spinal motor neuron involvement.The affected individuals carry homozygous PRUNE mutation (NM_021222.1,c.316G>A, p.D106N), showing the signs of spinal motor neuron involvementsupported by electrophysiological and muscle biopsy findings and alsopersistent high creatine kinase levels. We confirm that individuals with PRUNEmutations may have a major spinal motor neuron involvement as part of thePRUNE-associated neurodegenerative phenotype. The PRUNE gene should beconsidered in all the individuals with non-5q spinal muscular atrophy. Highcreatine kinase values may be a part of PRUNE disease spectrum.

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