Highcreatine kinase values may be a part of PRUNE disease spectrum.
📌 3 Key Takeaways
🎯
Objective & Hypothesis: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.
📊
Key Findings & Data: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.
💡
Conclusion & Impact:Highcreatine kinase values may be a part of PRUNE disease spectrum.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters
Özet
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.
🔖
Cite This Article
OKUR, D., DAİMAGÜLER, H. S., DANYELİ, A. E., TEKGÜL, H., WANG, H., WUNDERLİCH, G., ÇIRAK, S., YİŞ, U. (2019). Bi-allelic mutations in PRUNE lead to neurodegeneration with spinal motor neuron involvement and hyperCKaemia. Turkish Journal of Pediatrics, Cilt: 61 - Sayı: 6, 931–936. https://ajindex.com/articles/412004
Bilitou A, De Marco N, Bello AM, et al. Spatial and temporal expressions of prune reveal a role in Muller gliogenesis during Xenopus retinal development. Gene 2012; 509: 93-103
Kobayashi T, Hino S, Oue N, et al. Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions. Mol Cell Biol 2006; 26: 898-911
Karaca E, Harel T, Pehlivan D, et al. Genes that affect brain structure and function identified by rare variant analyses of mendelian neurologic disease. Neuron 2015; 88: 499-513
Zollo M, Ahmed M, Ferrucci V, et al. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. Brain 2017; 140: 940-952
Alawbathani S, Kawalia A, Karakaya M, Altmuller J, Nurnberg P, Cirak S. Late diagnosis of a truncating WISP3 mutation entails a severe phenotype of progressive pseudorheumatoid dysplasia. Cold Spring Harb Mol Case Stud 2018; 4: a002139
Iacomino M, Fiorillo C, Torella A, et al. Spinal motor neuron involvement in a patient with homozygous PRUNE mutation. Eur J Paediatr Neurol 2018; 22: 541-543
Eom TY, Roth KA, Jope RS. Neural precursor cells are protected from apoptosis induced by trophic factor withdrawal or genotoxic stress by inhibitors of glycogen synthase kinase 3. J Biol Chem 2007; 282: 22856-22864
Brooke MH, Engel WK. The histographic analysis of human muscle biopsies with regard to fiber types
Diseases of the upper and lower motor neuron. Neurology 1969; 19: 378-393
Costain G, Shugar A, Krishnan P, Mahmutoglu S, Laughlin S, Kannu P. Homozygous mutation in PRUNE1 in an Oji-Cree male with a complex neurological phenotype. Am J Med Genet Part A 2017; 173: 740-743
Karakaya M, Yilmaz S, Storbeck M, et al. PRUNE1: a disease-causing gene for secondary microcephaly. Brain 2017; 140: e61
Alfadhel M, Nashabat M, Hundallah K, Al Hashem A, Alrumayyan A, Tabarki B. PRUNE syndrome is a new neurodevelopmental disorder: report and review. Child Neurol Open 2018; 5: 2329048X17752237
Bahi-Buisson N, Poirier K, Fourniol F, et al. The wide spectrum of tubulinopathies: what are the key features for the diagnosis? Brain 2014; 137(Pt 6): 1676-1700
Rudnik-Schöneborn S, Lützenrath S, Borkowska J, Karwanska A, Hausmanowa-Petrusewicz I, Zerres K. Analysis of creatine kinase activity in 504 patients with proximal spinal muscular atrophy types I-III from the point of view of progression and severity. Eur Neurol 1998; 39: 154-162.