Peripheral synucleinopathy in a DJ1 patient with Parkinson disease, cataracts, and hearing loss.
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ABSTRACT:
SUBMITTER: Narendra DP
PROVIDER: S-EPMC6556091 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We analyzed the DJ1 gene in a large consecutive series (N=163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset ≤40 years of age) patients and 100 healthy controls (mean age 64 ± 7 years). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified.
| S-EPMC3878804 | biostudies-literature
Project description:IntroductionApproximately 10% of patients with Parkinson disease (PD) present with early-onset disease (EOPD), defined as diagnosis before 50 years of age. Genetic factors are known to contribute to EOPD, with most commonly observed mutations in PRKN, PINK1, and DJ1 genes. The aim of our study was to analyze the frequency of PRKN, PINK1, and DJ1 mutations in an EOPD series from 4 neighboring European countries: Czech Republic, Germany, Poland, and Ukraine.MethodsDiagnosis of PD was made based on UK Brain Bank diagnostic criteria in departments experienced in movement disorders (1 from Czech Republic, 1 from Germany, 9 from Poland, and 3 from Ukraine). EOPD was defined as onset at or before 50 years of age. Of the 541 patients recruited to the study, 11 were Czech, 38 German, 476 Polish, and 16 Ukrainian. All cohorts were fully screened with Sanger sequencing for PRKN, PINK1, and DJ1 and multiplex ligation-dependent probe amplification for exon dosage.ResultsPRKN homozygous or double heterozygous mutations were identified in 17 patients: 1 Czech (9.1%), 1 German (2.6%), 14 Polish (2.9%), and 1 Ukrainian (6.3%). PINK1 homozygous mutations were only identified in 3 Polish patients (0.6%). There were no homozygous or compound heterozygous DJ1 mutations in analyzed subpopulations. One novel variant in PRKN was identified in the Ukrainian series.ConclusionIn the analyzed cohorts, mutations in the genes PRKN, PINK1, and DJ1 are not frequently observed.
| S-EPMC8192481 | biostudies-literature
Project description:ObjectivesWe used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL) and to identify possible prognostic factors for predicting recovery of hearing loss.Study designA retrospective, multicenter trial was conducted.MethodsTwo hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipo-prostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients' initial visit to our clinic.ResultsIn all patients, elevated white blood cell (WBC) counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR) significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP) were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved.ConclusionsHigh fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset.
| S-EPMC4148242 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD.Methods and resultsUsing RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs.ConclusionCollectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.
| S-EPMC8202568 | biostudies-literature
Project description:BackgroundHearing loss (HL) is a well-known feature of Fabry disease (FD). Its presence and characteristics have mainly been studied in adult patients, while only limited data are available on the presence and degree of HL in children with FD. This prompted us to study hearing sensitivity in pediatric FD patients.MethodsAll available audiograms of the Dutch and Norwegian children with FD were retrospectively collected. First, hearing sensitivity was determined by studying hearing thresholds at low, high, and ultra-high frequencies in children with FD and comparing them to zero dB HL, i.e., healthy children. In addition, the presence and type of slight/mild HL (defined as hearing thresholds at low frequencies of 25-40 dB HL) and moderate to severe HL (hearing thresholds >40 dB HL) at first visit were analyzed. If available, follow-up data were used to estimate the natural course of hearing sensitivity and HL in children with FD.ResultsOne-hundred-thirteen audiograms of 47 children with FD (20 boys, median age at first audiogram 12.0 (range 5.1-18.0) years) were analyzed. At baseline, slight/mild or moderate to severe HL was present in three children (6.4%, 2 boys). Follow-up measurements showed that three additional children developed HL before the age of 18. Of these six children, five had sensorineural HL, most likely caused by FD. Compared to healthy children (zero dB HL), FD children showed increased hearing thresholds at all frequencies (p < 0.01), which was most prominent at ultra-high frequencies (>8 kHz). Hearing sensitivity at these ultra-high frequencies deteriorated in a period of 5 years of follow-up.ConclusionA minority of children with FD show slight/mild or moderate to severe HL, but their hearing thresholds are poorer than the reference values for normal-hearing children. Clinical trials in FD children should demonstrate whether HL can be prevented or reversed by early treatment and should specifically study ultra-high frequencies.
| S-EPMC5579138 | biostudies-literature
Project description:Idiopathic sudden sensorineural hearing loss (ISSHL) is a common otologic emergency whose cause is still unclear. The importance of blood lipids in the pathogenesis of ISSHL is widely reported in literature. In fact elevated levels of low density lipoprotein cholesterol (LDL), total cholesterol (TC) and apolipoprotein B (Apo-B) have been proposed as risk factors for this pathology. No correlation has been described between serum lipid parameters and the prognosis of ISSHL. Aim of the present study was to identify prognostic factors associated with hearing recovery in a group of patients affected by ISSHL. Ninety-four patients with the diagnosis of ISSHL hospitalized between March 2013 and October 2014 were included in this study. Patients' blood sampling and hearing assessments were carried out. Patients were divided into two groups as "recovered" and "unrecovered", according to their response to the treatment. We found a statistically significant higher level of total cholesterol in the unrecovered group compared to the recovered one (p = 0.03). None of the other routine laboratory parameters have shown a statistically significant difference between the patients successfully treated and patients with poor outcomes. Total cholesterol concentrations may be a prognostic factor for recovery in ISSHL and should be assessed together with routine tests in patients with this condition. The other routine laboratory parameters seem to have no effect on the development and prognosis of this pathology.
| S-EPMC4514871 | biostudies-literature
Project description:PurposeCisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy.MethodsUtilizing linear and logistic regression analyses on 1680 well-characterized cisplatin-treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities. Genome-wide association studies and gene-based analyses were performed on each phenotype.ResultsHearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self-reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork-related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10-6 ) in gene-based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort (p = 0.06; n = 606). Gene-based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10-6 ), encoding a signaling protein important in germ cell tumors.ConclusionsGenetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.
| S-EPMC9302309 | biostudies-literature
Project description:IntroductionWe present a case report of hearing loss in a patient with Waldenstrom macroglobulinemia (WM) receiving treatment with bortezomib.Case presentationOur patient developed sudden bilateral sensorineural hearing loss after receiving three doses of bortezomib. His hearing loss was irreversible and resulted in a cochlear implant.ConclusionHearing loss secondary to bortezomib is a known, but very rare, side effect. Hearing loss secondary to WM is also rare and has been described in case reports.
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Project description:Low copper and ceruloplasmin in serum are the diagnostic hallmarks for Menkes disease, Wilson disease, and aceruloplasminemia. We report on five patients from four unrelated families with these biochemical findings who presented with a lethal autosomal-recessive syndrome of congenital cataracts, hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous or compound heterozygous mutations for all affected subjects in SLC33A1 encoding a highly conserved acetylCoA transporter (AT-1) required for acetylation of multiple gangliosides and glycoproteins. The mutations were found to cause reduced or absent AT-1 expression and abnormal intracellular localization of the protein. We also showed that AT-1 knockdown in HepG2 cells leads to reduced ceruloplasmin secretion, indicating that the low copper in serum is due to reduced ceruloplasmin levels and is not a sign of copper deficiency. The severity of the phenotype implies an essential role of AT-1 in proper posttranslational modification of numerous proteins, without which normal lens and brain development is interrupted. Furthermore, AT-1 defects are a new and important differential diagnosis in patients with low copper and ceruloplasmin in serum.
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Project description: Not available
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