Episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome) caused by a novel mutation in ADPRHL2 (AHR3)
- 2 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Neurological Sciences
- Vol. 42 (9), 3871-3878
- https://doi.org/10.1007/s10072-021-05100-w
Abstract
The protein “ADP-Ribosylarginine Hydrolase-Like Protein 2” is encoded by ADPRHL2 and reverses ADP-ribosylation. Recently, mutations in ADPRHL2 were found to be associated with a very rare childhood onset severe neurodegeneration syndrome with episodic, stress-induced seizures, ataxia, and axonal neuropathy. In this study, we evaluate a novel mutation in ADPRHL2 leading to an unknown adult onset syndrome “episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome).” Four patients with episodic psychosis, ataxia, and motor neuropathy with pyramidal signs were included in this study. An index patient presented ataxia, postural tremor in the hands, and hallucinations at age 20 years, which had started after a viral infection. She improved within 3 months without any treatment. Her neurological exam revealed mild distal weakness, brisk DTRs, bilateral Babinski sign, impaired vibration sensation, position, and ataxia. Pes cavus and hammer toes were also noted. EMG revealed neurogenic changes in distal muscles and normal sensory nerve conduction studies. Cranial MRI was normal. She had three more severe episodes in recent years, and her neurologic findings got progressively worse. Two of her older sisters had much milder phenotypes. The phenotype of the fourth patient from an unrelated family was identical with the index patient. All affected patients had homozygous novel NM_017825.3:c.838G>A (p.Ala280Thr) mutations in a highly conserved region of ADPRHL2. Western blot analyses demonstrated that ADPRHL2 was not expressed in these patients. Here, we describe a novel mutation in ADPRHL2, which further expands the phenotypic and genetic spectrum of the patients harboring these mutations.Keywords
This publication has 22 references indexed in Scilit:
- DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and BeyondInternational Journal of Molecular Sciences, 2016
- PARP-1 involvement in neurodegeneration: A focus on Alzheimer’s and Parkinson’s diseasesMechanisms of Ageing and Development, 2015
- PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegenerationCell Communication and Signaling, 2010
- The Role of the Cerebellum in Cognition and Emotion: Personal Reflections Since 1982 on the Dysmetria of Thought Hypothesis, and Its Historical Evolution from Theory to TherapyNeuropsychology Review, 2010
- Poly (ADP-ribose) glycohydrolase (PARG) and its therapeutic potentialFrontiers in Bioscience-Landmark, 2009
- Poly(ADP-ribose): novel functions for an old moleculeNature Reviews Molecular Cell Biology, 2006
- Identification and Characterization of a Mammalian 39-kDa Poly(ADP-ribose) GlycohydrolaseJournal of Biological Chemistry, 2006
- Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1Nature, 2005
- The ataxia–oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4DNA Repair, 2004
- Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's diseaseBrain, 1999