Eye of the Tiger Sign and Very Late Onset in Dentatorubral-Pallidoluysian Atrophy.
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ABSTRACT:
SUBMITTER: Morgado J
PROVIDER: S-EPMC6353528 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
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Eye of the Tiger Sign and Very Late Onset in Dentatorubral-Pallidoluysian Atrophy.
Morgado Joana J Reimão Sofia S Coelho Miguel M Rosa Mário M MM Ferreira Joaquim J JJ Correia Guedes Leonor L
Movement disorders clinical practice 20150522 3
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Project description:BackgroundDentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterized by myoclonus, epilepsy, ataxia, and dementia. Diagnosis is challenging due to the heterogeneous presentation and symptomatic overlap with other spinocerebellar ataxias. Symptoms vary according to age of onset, with a mean age at onset of 31 years. A CAG repeat expansion in the ATN1 gene results in neuronal intranuclear inclusions, variable neuronal loss, and astrocytosis in the globus pallidus, dentate and red nuclei. No disease-modifying or curative treatments are currently available.MethodsWe performed an online literature search using PubMed for all articles published in an English Language format on the topics of DRPLA or ATN1 over the last 10 years. Where these articles cited other research as support for findings, or statements, these articles were also reviewed. Contemporary articles from related research fields (e.g., Huntington's Disease) were also included to support statements.ResultsForty-seven articles were identified, 10 were unobtainable and 10 provided no relevant information. The remaining 27 articles were then used for the review template: seven case reports, seven case series, six model system articles (one review article), four population clinical and genetic studies (one review article), two general review articles, and one human gene expression study. Other cited articles or research from related fields gave a further 42 articles, producing a total of 69 articles cited: 15 case series (including eight family studies), 14 model systems (one review article), 14 population clinical and genetic studies (two review articles), 10 case reports, eight clinical trials/guidelines, four genetic methodology articles, three general review articles, and one human gene expression study.DiscussionDRPLA remains an intractable, progressive, neurodegenerative disorder without effective treatment. Early recognition of the disorder may improve patient understanding, and access to services and treatments. Large-scale studies are lacking, but are required to characterize the full allelic architecture of the disorder in all populations and the heterogeneous phenotypic spectrum, including neuroimaging findings, possible biomarkers, and responses to treatment.
| S-EPMC6222020 | biostudies-literature
Project description:BackgroundDentatorubral-pallidoluysian atrophy is a rare autosomal dominant neurodegenerative disease. It is a rare disease in the world. Therefore, sharing clinical encounters of this case can deepen global awareness and understanding of the disease.Case presentationThe patient was a 34-year-old male of Han nationality who was unmarried. The patient was admitted owing to weakness of the left lower limb with walking instability for 2 months and aggravation for 1 month. There was no dizziness, headache, numbness of limbs, convulsions, nausea, vomiting, abdominal pain, ataxia, nausea, vomiting, or abdominal pain. No nausea, vomiting, diarrhea, abdominal distension, tinnitus, hearing loss, fever, cough, expectoration. Personal history: worked in Cambodia 5 years ago, worked in Dubai 3 years ago, engaged in computer work, smoking or drinking habits. The patient was unmarried. Family history: the mother had symptoms similar to walking unsteadily (undiagnosed). Positive signs include a wide-base gait with a rotatory nystagmus that jumps upward in both eyes. Bilateral finger-nose instability test was quasi-positive, rapid alternating test was negative, and eye closure tolerance test was positive. Tendon reflexes were active in both upper limbs and hyperreflexia in both lower limbs. Stability of the heel, knee, and tibia. Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. The patient was diagnosed with dentatorubral-pallidoluysian atrophy. Dentatorubral-pallidoluysian atrophy remains a progressive neurodegenerative disease with no effective treatment. At present, the proband is taking 5 mg of buspirone three times a day, which has been reported to improve the symptoms. The patient was followed up for 6 months after taking buspirone, and there was no significant improvement in the temporary symptoms. At present, there are few cases of dentatorubral-pallidoluysian atrophy, and the characteristics of nystagmus in this disease have not been proposed in the past. This case reported the unusual presentation of nystagmus.ConclusionDentatorubral-pallidoluygur atrophy is a rare neurodegenerative disease with autosomal dominant inheritance. To the best of our knowledge, our present case report is the first case report of dentatorubral-pallidoluygur atrophy with specific nystagmus. We describe the special eye shake and its positive signs to increase dentatorubral-pallidoluysian atrophy clinical positive signs.
| S-EPMC11378363 | biostudies-literature
Project description: Not available
| S-EPMC11892984 | biostudies-literature
Project description:IntroductionDentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with various neurological manifestations. Corneal endothelial degeneration and optic atrophy have been reported separately; however, there are no reports of corneal endothelial degeneration with optic atrophy.CasesHerein, we present four related patients with DRPLA: two patients (69-year-old woman and 80-year-old man) who exhibited both corneal endothelial degeneration and optic atrophy and another two (49- and 51-year-old women, respectively) who exhibited only corneal endothelial degeneration. We quantified the reduction in corneal endothelial cell density (ECD) and hexagonality using specular microscopy and thinning of the circumpapillary retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT).ConclusionThis is the first report of DRPLA accompanied by corneal endothelial degeneration and/or optic atrophy, which were both quantified based on the corneal ECD and the circumpapillary RNFL thickness using specular micrography and OCT, respectively. The pathophysiological mechanism is unclear; however, the involvement of the nuclear receptor TLX interacting with atrophin-1 may be implicated in ophthalmic manifestations of DRPLA. Therefore, we recommend performing specular micrography and/or OCT when patients with DRPLA experience visual disturbances.
| S-EPMC9513026 | biostudies-literature
Project description:Dentatorubral-pallidoluysian atrophy (DRPLA) is a polyglutamine neurodegenerative disorder caused by CAG expansions in ATN1. To investigate its pathogenesis, we developed and characterized Drosophila models expressing human ATN1 with normal (Q7) or pathogenic (Q88) repeats.
2025-02-11 | GSE289036 | GEO
Project description:Dentatorubral-pallidoluysian atrophy (DRPLA) is caused by DRPLA protein which carries expansion of a glutamine repeat. Abnormal high-molecular-mass complex formation by DRPLA protein and its pathological ubiquitination comprise the disease processes in the brains of patients with DRPLA. In this study, DRPLA protein complex was isolated and shown to have pathologically stronger bond formation with DRPLA proteins in DRPLA brain tissue compared with control brain tissue. Immunochemical methods and an enzymic dephosphorylation technique were used to demonstrate that DRPLA protein complex is aberrantly phosphorylated in DRPLA brain tissue. Immunohistochemical studies show that both the ubiquitinated cytoplasmic inclusions and the nuclear membrane are aberrantly phosphorylated in DRPLA-affected neurons. This finding suggests that the nuclear membrane is another pathological focus of DRPLA neurodegeneration.
| S-EPMC1221397 | biostudies-other
Project description:A 68-year-old male patient presented to the neurology clinic with tremor, lightheadedness, and a history of syncope. Exam showed mild Parkinsonism. Neuroimaging revealed symmetric lesions of the globus pallidus (the eye-of-the-tiger sign) concerning for neurodegeneration with brain iron accumulation (NBIA). Genetic panel for NBIA was ordered, specifically pantothenate kinase-associated neurodegeneration (PKAN), including pantothenate kinase 2 (PanK2) - the genetic marker for the pantothenate kinase enzyme.
| S-EPMC6695239 | biostudies-literature
Project description:BackgroundIn premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO).MethodsAt three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO.ResultsWe analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821.ConclusionIn VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.
| S-EPMC8316489 | biostudies-literature
Project description:Autosomal dominant dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) are neurodegenerative disorders caused by CAG trinucleotide repeat expansions. An inverse correlation of age at onset with the length of the expanded CAG trinucleotide repeats has been demonstrated, and the intergenerational instability of the length of the CAG trinucleotide repeats, which is more prominent in paternal than in maternal transmissions, has been shown to underlie the basic mechanisms of anticipation in DRPLA and MJD. Our previous observations on DRPLA and MJD pedigrees, as well as a review of the literature, have suggested that the numbers of affected offspring exceed those of unaffected offspring, which is difficult to explain by the Mendelian principle of random segregation of alleles. In the present study, we analyzed the segregation patterns in 211 transmissions in 24 DRPLA pedigrees and 80 transmissions in 7 MJD pedigrees, with the diagnoses confirmed by molecular testing. Significant distortions in favor of transmission of the mutant alleles were found in male meiosis, where the mutant alleles were transmitted to 62% of all offspring in DRPLA (chi2 = 7.69; P<.01) and 73% in MJD (chi2 = 6.82; P<.01). The results were consistent with meiotic drive in DRPLA and MJD. Since more prominent meiotic instability of the length of the CAG trinucleotide repeats is observed in male meiosis than in female meiosis and meiotic drive is observed only in male meiosis, these results raise the possibility that a common molecular mechanism underlies the meiotic drive and the meiotic instability in male meiosis.
| S-EPMC1914673 | biostudies-other
Project description:Dentatorubral–pallidoluysian atrophy (DRPLA) is a devastating genetic disease presenting myoclonus, epilepsy, ataxia, and dementia. DRPLA is caused by the expansion of a CAG repeat in the ATN1 gene. The expanded CAG repeats are unstable, and ongoing repeat expansions contribute to disease onset, progression and severity. Previously, we characterized a small molecule, naphthyridine–azaquinolone (NA), which binds to CAG slip-out structures and induces repeat contraction in Huntington’s disease mice. Here, we demonstrate that long-term intracerebroventricular infusion of NA leads to repeat contraction in a murine model of DRPLA. To identify the effects of NA on transcriptional regulation, we conducted comprehensive gene expression analysis using RNA sequencing (RNA-Seq) in striatum from PBS-treated and NA-treated DRPLA mice.
2022-09-08 | GSE183652 | GEO