Search results for " Dyskinesia"
showing 10 items of 46 documents
Development and validation of a method of cilia motility analysis for the early diagnosis of primary ciliary dyskinesia.
2011
Background: Primary ciliary dyskinesia (PCD) is a clinically uniform entity, but cilia motility and structure can vary between patients, making the diagnosis difficult. The aim of this study was to evaluate the sensitivity and specificity in diagnosing PCD of a system of high-resolution digital high-speed video analysis with proprietary software that we developed for analysis of ciliary motility (Desinsoft-Bio 200). The secondary aim was to correlate nasal ciliary activity with clinical and structural abnormalities in PCD. Material and methods: We analysed nasal mucociliary transport, cilia ultrastructure, nasal ciliary beat frequency and beat pattern studied by high-resolution digital high…
Ultrastructural patterns of primary ciliar dyskinesia syndrome.
2005
Clinical presentation, ciliary ultrastructure, and nasal mucociliary transport by a radioisotopic technique were analyzed in 14 Kartagener syndrome patients. In this study the most common pattern was the absence of outer and inner dynein arms in 57% of cases. Also reported are 14% patients with short inner dynein arms. A total of 29% of the patients showed normal dynein arms. Mucociliary stasis was observed in 13 cases. Primary ciliary dyskinesia syndrome and Kartagener syndrome are clinically homogeneous and morphologically heterogeneous. The authors conclude that a typical clinical presentation with an altered mucociliary transport obtained by radioisotopic technique is diagnostic althoug…
Mutations in ARL2BP, Encoding ADP-Ribosylation-Factor-Like 2 Binding Protein, Cause Autosomal-Recessive Retinitis Pigmentosa
2013
Retinitis pigmentosa (RP) is a genetically heterogeneous retinal degeneration characterized by photoreceptor death, which results in visual failure. Here, we used a combination of homozygosity mapping and exome sequencing to identify mutations in ARL2BP, which encodes an effector protein of the small GTPases ARL2 and ARL3, as causative for autosomal-recessive RP (RP66). In a family affected by RP and situs inversus, a homozygous, splice-acceptor mutation, c.101−1G>C, which alters pre-mRNA splicing of ARLBP2 in blood RNA, was identified. In another family, a homozygous c.134T>G (p.Met45Arg) mutation was identified. In the mouse retina, ARL2BP localized to the basal body and cilium-associated…
A functional study of the esophagus in patients with non-cardiac chest pain and dysphagia.
2015
Background/Aims: Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest pain (NCCP), with gastroesophageal reflux in 60% of cases. Achalasia and diffuse esophageal spasm are the most frequent anomalies described in patients with dysphagia. The goal of this study was to evaluate the occurrence of esophageal body and lower esophageal sphincter motor abnormalities in patients with dysphagia, NCCP, or both. Materials and Methods: This study is a retrospective analysis of 716 patients with NCCP and/or dysphagia tested between January 1994 and December 2010. 1023 functional studies were performed, 707 of which were esophageal manometries, 225 esophageal …
New adenylate kinase 7 (AK7) mutation in primary ciliary dyskinesia.
2012
Background Primary ciliary dyskinesia (PCD) is a congenital hereditary disease affecting 1/20,000–60,000 people that causes chronic sinusitis, bronchiectasis, sinus hypoplasia, secretory otitis media, and low fertility. The complexity and heterogeneity of the disease make diagnosis difficult. Although the genetic origin of PCD is clear, mutations in only five genes have been associated with the disease, and, to date, no disease-causing gene has been identified. Recently, low levels of AK7 gene expression have been linked to PCD. This study was designed to determine the mutational status of the AK7 gene in 31 PCD (17 PCD and 14 Kartagener syndrome diagnosed) patients compared with 40 healthy…
Role of adenylate kinase type 7 expression on cilia motility: possible link in primary ciliary dyskinesia.
2010
Background Adenylate kinase 7 (AK7) mediates the reaction 2ADP ↔ ATP + AMP, providing energy for the beating of cilia. A study recently showed that AK7 expression may be correlated with the primary ciliary dyskinesia (PCD) phenotype in mice. In this study, we characterized AK7 expression in vitro in an air–liquid interface (ALI) model and in middle nasal turbinate biopsy specimens from a cohort of patients with PCD to elucidate whether AK7 expression is correlated with ciliary malfunction. Methods AK7 expression was measured by real-time reverse-transcription polymerase chain reaction and Western blotting. In vitro differentiated nasal human epithelial cell siRNA experiments were performed …
Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease
2009
BACKGROUND: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis. METHODS: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits…
Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?
2020
Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical tria…
Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort
2021
AbstractAim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson’s disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dos…
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurologi…
2019
Abstract KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the …