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1.
Ziv Gan-Or Christopher Liong Roy N. Alcalay 《Current neurology and neuroscience reports》2018,18(8):44
Purpose of Review
GBA mutations are the most common known genetic cause of Parkinson’s disease (PD). Its biological pathway may be important in idiopathic PD, since activity of the enzyme encoded by GBA, glucocerebrosidase, is reduced even among PD patients without GBA mutations. This article describes the structure and function of GBA, reviews recent literature on the clinical phenotype of GBA PD, and suggests future directions for research, counseling, and treatment.Recent Findings
Several longitudinal studies have shown that GBA PD has faster motor and cognitive progression than idiopathic PD and that this effect is dose dependent. New evidence suggests that GBA mutations may be important in multiple system atrophy. Further, new interventional studies focusing on GBA PD are described. These studies may increase the interest of PD patients and caregivers in genetic counseling.Summary
GBA mutation status may help clinicians estimate PD progression, though mechanisms underlying GBA and synucleinopathy require further understanding.2.
Wu YR Chen CM Chao CY Ro LS Lyu RK Chang KH Lee-Chen GJ 《Journal of neurology, neurosurgery, and psychiatry》2007,78(9):977-979
Background
Mutations in the glucocerebrosidase (GBA) gene have recently been identified as contributing to the development of Parkinson disease (PD) in Ashkenazi Jews.Methods
To investigate whether this finding can be confirmed in a Taiwanese population, we conducted a case control study in a cohort of 518 PD patients and 339 controls for the three common GBA mutations in Taiwan, L444P, RecNciI and R120W, using PCR restriction enzyme assay and DNA sequencing.Results
Heterozygous GBA mutations were detected in 16 PD patients (3.1%) and four controls (1.2%). Although this difference was not statistically significant (p = 0.0703), the average age at disease onset of the 16 PD patients (50.6 (12.3) years) was significantly younger than that of the total patient group (63.8 (10.5) years; p = 0.0007) and the non‐carrier patient group (64.2 (10.2) years; p = 0.0005). After stratification by age, the frequency of mutation carriers was significantly higher for the early onset PD (EOPD, age at onset ⩽50 years) group than for age matched controls (12.9% vs 1.8%; p = 0.0335) and there was a trend towards an increased risk of the mutation carrier with EOPD (odds ratio 8.30; 95% CI 1.45 to 156.53). Clinically, all 16 patients carrying a GBA mutation presented with a typical parkinsonian phenotype and experienced a good or excellent response to levodopa.Conclusions
Mutations of the GBA gene may be associated with the development of EOPD in Taiwan.Parkinson disease (PD) is the second most common neurodegenerative disease, characterised by resting tremor, bradykinesia, rigidity and postural instability. These symptoms result predominantly from selective loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of dopamine in their projections. Pathologically, PD is defined by the presence of Lewy bodies, intracellular neuronal inclusions in the substantia nigra pars compacta and other brain sites.1 The pathogenesis of PD remains unclear. An interaction between environmental factors and genetic predisposition is thought to contribute to disease development.2 Causal mutations in the genes for α‐synuclein, parkin, DJ‐1, PTEN induced kinase 1 and leucine‐rich repeat kinase‐2 have been identified.3 However, mutations of these genes do not account for the occurrence of PD in all patients. Identifying novel PD genetic risk factors is important to understand its pathogenesis.Gaucher disease (GD) is a recessively inherited glycolipid storage disorder caused by deficiency of the lysosomal enzyme glucocerebrosidase (GBA).4 Clinically, GD is characterised by vast phenotypic heterogeneity and is classified into three types based on the severity of associated neurological symptoms.5 Recent studies have reported genetic association between GD and PD.6,7 The molecular pathogenic mechanism causing PD in GBA mutation carriers remains unclear.The gene encoding GBA has been localised at chromosome 1q21, and there is a highly homologous pseudogene (GBAP) sequence located 16 kb downstream.8 More than 200 mutations, including point mutations, deletions and rearrangements, have been identified in this gene (http://www.hgmd.cf.ac.uk/ac/gene.php?gene = GBA). Mutation analysis of GD patients in Taiwan has reported three common mutations, L444P, RecNciI (the recombination allele between the GBA and GBAP genes) and R120W, that account for 87% of Gaucher chromosomes.9 R120W was defined as a mild mutation associated with non‐neuropathic GD in Taiwanese.9To investigate the possible association between the GBA gene mutations and PD in Taiwan, we examined the frequency of these three GBA mutations to determine whether the GBA mutations are genetically associated with PD, using a case control study design. 相似文献3.
Karen A.G. Takazaki Thiago Junqueira R. Rezende Alberto R.M. Martinez Carelis Gonzalez-Salazar Anamarli Nucci Iscia Lopes-Cendes Marcondes C. França 《Clinical neurophysiology》2018,129(11):2290-2295
Objectives
To evaluate autonomic symptoms and function in Friedreich’s Ataxia (FRDA).Methods
Twenty-eight FRDA patients and 24 controls underwent clinical/electrophysiological testing. We employed the Friedreich’s Ataxia Rating Scale (FARS) and the Scales for Outcomes in Parkinson’s Disease: Autonomic Questionnaire-SCOPA-AUT to estimate the intensity of ataxia and autonomic complaints, respectively. Cardiovagal tests and the quantitative sudomotor axonal reflex, Q-SART, were then assessed in both groups.Results
In the patient group, there were 11 men with mean age of 31.5?±?11.1?years. Mean SCOPA-AUT score was 15.1?±?8.1. Minimum RR interval at rest was shorter in the FRDA group (Median 831.3?×?724.0?ms, p?<?0.001). The 30:15 ratio, Valsalva index, E:I ratio, low and high frequency power presented no differences between patients and controls (p?>?0.05). Sweat responses were significantly reduced in patients for all sites tested (forearm 0.389?×?1.309?µL; proximal leg 0.406?×?1.107?µL; distal leg 0.491?×?1.232?µL; foot 0.265?×?0.708?µL; p value?<?0.05). Sweat volumes correlated with FARS scores.Conclusions
We found abnormal sudomotor but normal heart rate variability in FRDA. Small cholinergic post-ganglionic fibers are affected in the disease.Significance
Quantification of sudomotor function might be a biomarker for FRDA. 相似文献4.
5.
Kristin Aaser Lunde Janete Chung Ingvild Dalen Kenn Freddy Pedersen Jan Linder Magdalena E. Domellöf Eva Elgh Angus D. Macleod Charalampos Tzoulis Jan Petter Larsen Ole-Bjørn Tysnes Lars Forsgren Carl E. Counsell Guido Alves Jodi Maple-Grødem 《Alzheimer's & dementia》2018,14(10):1293-1301
Introduction
Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.Methods
Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.Results
A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.Discussion
GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles. 相似文献6.
Karim Benmouna Christophe Milants François Charles Wang 《Clinical neurophysiology》2018,129(2):341-344
Objective
The aim of this study was to evaluate how the motor unit number index (MUNIX) is related to the adapted multiple point stimulation (AMPS) technique.Methods
MUNIX and AMPS technique were prospectively performed on thenar muscles in 20 consecutive patients referred to our neurophysiological laboratory with the clinical diagnosis of a possible motoneurone disorder (MND). The clinical and paraclinical assessment confirmed the diagnosis of MND in 13 out of 20 patients, amyotrophic lateral sclerosis (ALS) in 9 (with MND group). In the other 7 patients, there were neither evidence of MND, nor of any peripheral nervous system disease (without MND group).Results
AMPS and MUNIX data were significantly (p?<?0.001) lower in patients with MND than in patients without MND. There was a strong significant positive linear correlation between AMPS and MUNIX values (n?=?20; R?=?0.83; p?<?0.01).Conclusion
Both MUNIX and AMPS methods could serve as a reliable marker to document the motor unit loss.Significance
The present paper constitutes one more clue of MUNIX reliability. 相似文献7.
Sarah Schnitzler Christian Johannes Hartmann Stefan Jun Groiss Lars Wojtecki Alfons Schnitzler Jan Vesper Jan Hirschmann 《Clinical neurophysiology》2018,129(5):959-966
Objective
To assess whether high frequency oscillations (HFOs, >150?Hz), known to occur in basal ganglia nuclei, can be observed in the thalamus.Methods
We recorded intraoperative local field potentials from the ventral intermediate nucleus (VIM) of the thalamus in patients with Essential Tremor (N?=?16), Parkinsonian Tremor (3), Holmes Tremor (2) and Dystonic Tremor (1) during implantation of electrodes for deep brain stimulation. Recordings were performed with up to five micro/macro-electrodes that were simultaneously advanced to the stereotactic target.Results
Thalamic HFOs occurred in all investigated tremor syndromes. A detailed analysis of the Essential Tremor subgroup revealed that medial channels recorded HFOs more frequently than other channels. The highest peaks were observed 4?mm above target. Macro- but not microelectrode recordings were dominated by peaks in the slow HFO band (150–300?Hz), which were stable across several depths and channels.Conclusion
HFOs occur in the thalamus and are not specific to any of the tremors investigated. Their spatial distribution is not homogeneous, and their appearance depends on the type of electrode used for recording.Significance
The occurrence of HFOs in the thalamus of tremor patients indicates that HFOs are not part of basal ganglia pathophysiology. 相似文献8.
Background
Aromatic l-amino acid decarboxylase (AADC) deficiency (OMIM #608643) is a rare and severe disorder of biogenic amine synthesis caused by mutations in the DDC gene. The phenomenology of the movement disorder includes intermittent oculogyric crises and limb dystonia, generalized athetosis, and impaired voluntary movement.Objective
To identify clinical manifestations and DDC gene mutations in two Chinese mainland children who are siblings with AADC deficiency.Methods
We used targeted next-generation sequencing and quantitative polymerase chain reaction (qPCR) to reveal DDC mutations in these children.Results
Two DDC gene mutations were found: one missense mutation, c.1040G?>?A (p.Arg347Gln), is a reported mutation derived from the mother; the other mutation, a whole-exon 11 and 12 deletion, is a novel mutation derived from the father. The index patient and her brother both had poor sucking power and feeding difficulty at birth and episodes of oculogyric crises, truncal hypotonia, limb hypertonia, sleep disturbances, irritability, and motor delay. The siblings both died at 1?year and 10?months due to asphyxia and pneumonia during gaze and hypertonia episodes.Conclusion
This study identified a novel DDC gene deletion mutation in two siblings with AADC deficiency disease in the Chinese mainland population. 相似文献9.
Niraj K. Sharma Carlos Pedreira Maria Centeno Umair J. Chaudhary Tim Wehner Lucas G.S. França Tinonkorn Yadee Teresa Murta Marco Leite Sjoerd B. Vos Sebastien Ourselin Beate Diehl Louis Lemieux 《Clinical neurophysiology》2017,128(7):1246-1254
Objective
To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data.Method
Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs. First, we determined whether WC-human agreement variability falls within inter-reviewer agreement variability by calculating the variation of information for each classifier pair and quantifying the overlap between all WC-reviewer and all reviewer-reviewer pairs. Second, we compared WC and EEG reviewers’ spike identification and individual spike class labels visually and quantitatively.Results
The overlap between all WC-human pairs and all human pairs was >80% for 3/5 patients and >58% for the other 2 patients demonstrating WC falling within inter-human variation. The average sensitivity of spike marking for WC was 91% and >87% for all three EEG reviewers. Finally, there was a strong visual and quantitative similarity between WC and EEG reviewers.Conclusions
WC performance is indistinguishable to that of EEG reviewers’ suggesting it could be a valid clinical tool for the assessment of IEDs.Significance
WC can be used to provide quantitative analysis of epileptic spikes. 相似文献10.
Lin-Mei Chiang Go-Shine Huang Chi-Chin Sun Ying-Li Hsiao Chung Kun Hui Mei-Hua Hu 《Brain & development》2018,40(9):775-780
Purpose
Epilepsy is an important neurological condition that frequently associated with neurobehavioral disorders in childhood. Our aim was to identify the risk of developing epilepsy subsequent to febrile seizure and the association between epilepsy risk factors and neurobehavioral disorders.Subjects and methods
This longitudinal population-based cohort data included 952 patients with a febrile seizure diagnosis and 3808 age- and sex-matched controls. Participants were recruited for the study from 1996 to 2011, and all patients were followed up for maximum 12.34?years.Results
The association of epilepsy was significantly higher (18.76-fold) in individuals that experienced febrile seizure compared to controls. Further, of those individuals who experienced febrile seizure, the frequency of subsequent development of epilepsy was 2.15-fold greater in females, 4.846-fold greater in patients with recurrent febrile seizure, and 11.26-fold greater patients with comorbid autism.Conclusions
Our study showed that being female, comorbid autism with febrile seizure and recurrent febrile seizure had an increased association with development of epilepsy. Increased recognition the association for epilepsy might be warranted in those febrile seizure children with certain characteristics. 相似文献11.
Tomoyuki Fumuro Masao Matsuhashi Riki Matsumoto Kiyohide Usami Akihiro Shimotake Takeharu Kunieda Takayuki Kikuchi Kazumichi Yoshida Ryosuke Takahashi Susumu Miyamoto Akio Ikeda 《Clinical neurophysiology》2018,129(9):1884-1890
Objective
Neuro-feedback (NFB) training by the self-regulation of slow potentials (SPs) <0.5?Hz recorded from the vertex scalp has been applied for seizure suppression in patients with epilepsy. However, SP is highly susceptible to artifact contamination, such as the galvanic skin response (GSR). This study aimed to evaluate the correlation between SPs recorded from the scalp and intracranial electroencephalography (EEG) by event-related coherence analysis.Methods
The scalp and subdural SPs were simultaneously recorded during NFB training by the DC-EEG machine while undergoing invasive recordings before epilepsy surgery in 10 patients with refractory partial epilepsy. The SPs at the vertex electrode were used as a reference for coherence analysis.Results
The coherence of SPs negatively correlated with the distance between the subdural and scalp electrodes. A significant negative correlation was noted between the linear subdural–scalp electrode distance and the coherence value (r?=????0.916, p?<?0.001).Conclusion
Scalp-recorded SPs from the vertex area primarily reflect the cortical activity of high lateral convexity.Significance
Our results strongly suggest that SPs in NFB recorded from the vertex scalp electrode is derived from the cortices of high lateral convexity but not from the artifacts, such as GSR. 相似文献12.
Sang-Ku Park Byung-Euk Joo Seunghoon Lee Jeong-A. Lee Jeong-Ho Hwang Doo-Sik Kong Dae-Won Seo Kwan Park Hoon-Taek Lee 《Clinical neurophysiology》2018,129(5):1097-1102
Objective
The aim of this study was to define the critical warning sign of real-time brainstem auditory evoked potential (BAEP) for predicting hearing loss (HL) after microvascular decompression (MVD) for hemifacial spasm (HFS).Methods
Nine hundred and thirty-two patients with HFS who underwent MVD with intraoperative monitoring (IOM) of BAEP were analyzed. We used a 43.9?Hz/s stimulation rate and 400 averaging trials to obtain BAEP. To evaluate HL, pure-tone audiometry and speech discrimination scoring were performed before and one week after surgery. We analyzed the incidence for postoperative HL according to BAEP changes and calculated the diagnostic accuracy of significant warning criteria.Results
Only 11 (1.2%) patients experienced postoperative HL. The group showing permanent loss of wave V showed the largest percentage of postoperative HL (p?<?0.001). No patient who experienced only latency prolongation (≥1?ms) had postoperative HL. Loss of wave V and latency prolongation (≥1?ms) with amplitude decrement (≥50%) were highly associated with postoperative HL.Conclusions
Loss of wave V and latency prolongation of 1?ms with amplitude decrement ≥50% were the critical warning signs of BAEP for predicting postoperative HL.Significance
These findings elucidate the critical warning sign of real-time BAEP. 相似文献13.
Xiaoling Yang Ping Qian Xiaojing Xu Xiaoyan Liu Xiru Wu Yuehua Zhang Zhixian Yang 《Brain & development》2018,40(3):205-210
Objective
Epilepsy-aphasia spectrum (EAS) are a group of epilepsy syndromes denoting an association between epilepsy, speech disorders and the EEG signature of centrotemporal spikes. Mutations in the GRIN2A gene, encoding the NMDA glutamate receptor α2 subunit were reported in focal epilepsy with speech disorder. We aimed to explore the role of GRIN2A mutations in patients with centrotemporal spikes related epileptic syndromes in a Chinese cohort.Methods
Patients with Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), atypical benign partial epilepsy (ABPE), and benign epilepsy with centrotemporal spikes (BECTS) were recruited. GRIN2A mutation screening was performed using PCR and Sanger sequencing.Results
122 patients, including 9 LKS, 26 ECSWS, 42 ABPE and 45 BECTS were enrolled. The mean age of seizure or aphasia onset was 5?years, ranging from 10?months to 11?years. Heterozygous GRIN2A mutations were detected in four patients (G760S, D1385Y, C455Y and C231R) GRIN2A mutation was found in 11.1% (1 out of 9 cases) of LKS, and in 7.1% (3 out of 42 cases) of ABPE, but in none with ECSWS and BECTS. No GRIN2A mutation was found in patients with a family history of febrile seizures or epilepsy.Conclusion
GRIN2A mutation is a genetic cause in less than 11% patients with LKS or ABPE. GRIN2A gene is a rare causative gene in Chinese patients with EAS, suggesting the possibility of other gene involved in the pathogenesis. 相似文献14.
Alexander Grimm Hubertus Axer Bianka Heiling Natalie Winter 《Clinical neurophysiology》2018,129(7):1403-1409
Objective
Reference values are crucial for nerve ultrasound. Here, we reevaluated normal nerve and fascicle cross-sectional area (CSA) values in humans and compared them to published values. Based on these data, ultrasound pattern sum score (UPSS) boundary values were revisited and readjusted.Methods
Ultrasound of different peripheral nerves was performed in 100 healthy subjects at anatomically defined landmarks. Correlations with age, gender, height and weight were calculated.Results
Overall, correspondence to other published reference values was high. Gender-dependency was found for the proximal median nerve. Dependency from height occurred in the tibial nerve (TN). Weight-dependency was not found. However, the most obvious differences were found in the TN between men >60?years and women <60?years. Thus, general boundary values were defined using the mean plus the twofold standard deviation for all subjects and nerve segments except for the TN, in which different cut-offs were proposed for elder men. Accordingly, the cut-offs for the UPSS were re-adjusted, none of the individuals revealed more than 2 points at maximum.Conclusions
The influence of distinct epidemiological factors on nerve size is most prominent in the TN, for which thus several normal values are useful.Significance
Adjusted reference values improve the accuracy of the UPSS. 相似文献15.
Saori Miyagishima Tadayoshi Asaka Kaori Kamatsuka Naoki Kozuka Masaki Kobayashi Lisa Igarashi Tsukasa Hori Hiroyuki Tsutsumi 《Brain & development》2018,40(8):627-633
Aims
We conducted a longitudinal cohort study to analyze the relationship between outcome of gross motor development in preterm infants and factors that might affect their development.Methods
Preterm infants with a birth weight of <1500?g were recruited. We measured spontaneous antigravity limbs movements by 3D motion capture system at 3?months corrected age. Gross motor developmental outcomes at 6 and 12?months corrected age were evaluated using the Alberta Infant Motor Scale (AIMS). Statistical analysis was carried out by canonical correlation analysis.Results
Eighteen preterm infants were included. In the 6?months corrected age analysis, spontaneous movement had a major effect on Prone and Sitting at 6?months corrected age of AIMS. In the 12?months corrected age analysis, spontaneous movement had a major effect on Sitting and Standing at 12?months corrected age of AIMS.Conclusions
In preterm infants, better antigravity spontaneous movements at 3?months corrected age were significantly correlated with better gross motor development at 6 or 12?months corrected age. 相似文献16.
João Castelhano Paula Tavares Susana Mouga Guiomar Oliveira Miguel Castelo-Branco 《Clinical neurophysiology》2018,129(5):981-989
Objective
Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures can be used as potential biomarkers in autism spectrum disorder (ASD).Methods
We studied an extensive set of stimuli (9 categories of faces) and performed data driven classification (Support vector machine, SVM) of ASD vs. Controls with features based on the EEG power responses. We carried out an extensive time-frequency and synchrony analysis of distinct face categories requiring different processing mechanisms in terms of non-holistic vs. holistic processing.Results
We found that the neuronal oscillatory responses of low gamma frequency band, locked to photographic and abstract two-tone (Mooney) face stimulus presentation are decreased in ASD vs. the control group. We also found decreased time-frequency (TF) responses in the beta band in ASD after 350?ms, possibly related to motor preparation. On the other hand, synchrony in the 30–45?Hz band showed a distinct spatial pattern in ASD. These power changes enabled accurate classification of ASD with an SVM approach. SVM accuracy was approximately 85%. ROC curves showed about 94% AUC (area under the curve). Combination of Mooney and Photographic face stimuli evoked features enabled a better separation between groups, reaching an AUC of 98.6%.Conclusion
We identified a relative decrease in EEG responses to face stimuli in ASD in the beta (15–30?Hz; >350?ms) and gamma (30–45?Hz; 55–80?Hz; 50–350?ms) frequency ranges. These can be used as input of a machine learning approach to separate between groups with high accuracy.Significance
Future studies can use EEG time-frequency patterns evoked by particular types of faces as a diagnostic biomarker and potentially as outcome measures in therapeutic trials. 相似文献17.
Maria-Ioanna Stefanou Debora Desideri Justus Marquetand Paolo Belardinelli Christoph Zrenner Holger Lerche Ulf Ziemann 《Clinical neurophysiology》2017,128(12):2503-2509
Objective
Mutations in STX1B encoding the presynaptic protein syntaxin-1B are associated with febrile seizures with or without epilepsy. It is unclear to what extent these mutations are linked to abnormalities of cortical glutamatergic or GABAergic neurotransmission. We explored this question using single- and paired-pulse transcranial magnetic stimulation (TMS) excitability markers.Methods
We studied nine currently asymptomatic adult STX1B mutation carriers with history of epilepsy and febrile seizures, who had been seizure-free for at least eight years without antiepileptic drug treatment, and ten healthy age-matched controls. Resting motor threshold (RMT), and input-output curves of motor evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI, marker of GABAAergic excitability) and intracortical facilitation (ICF, marker of glutamatergic excitability) were tested.Results
RMT, and input-output curves of MEP amplitude, SICI and ICF revealed no significant differences between STX1B mutation carriers and healthy controls.Conclusions
Findings suggest normal motor cortical GABAAergic and glutamatergic excitability in currently asymptomatic STX1B mutation carriers.Significance
TMS measures of motor cortical excitability show utility in demonstrating normal excitability in adult STX1B mutation carriers with history of seizures. 相似文献18.
Daiki Kondo Atsuko Noguchi Ikuko Takahashi Hiroki Kubota Tamami Yano Yoko Sato Miyuki Toyono Yukio Sawaishi Tsutomu Takahashi 《Brain & development》2018,40(9):760-767
Objective
To reveal a molecular lesion in the ZC4H2 gene in a Japanese family with arthrogryposis multiplex congenita (AMC) and intellectual disability (ID), and to characterize clinical features of patients with ZC4H2 gene mutations through a literature review.Patients
The probands are male siblings. The elder brother is an 11-year-old boy who showed AMC and ID and frequent postprandial hypoglycemia since 3?years of age. The younger brother also showed AMC, ID, and subclinical postprandial hypoglycemia. The boys’ mother also showed a minor malformation of the left toes.Method and result
Using Sanger sequencing, a hemizygous one base substitution designated c.627G?>?C, which is predicted to substitute asparagine for lysine at amino acid residue 209 (K209N), was identified in the siblings. The mother was heterozygous for this mutation. In silico analysis predicted K209N to be a constituent of a motif required for subcellular localization of the ZC4H2 protein in the nucleus. Transient expression studies of subcellular localization in COS-7 cells showed that compared to the wild-type protein, the transport of the mutant protein into the nucleus was inhibited, thus confirming K209N as a molecular lesion in this family. The literature reviews revealed postprandial hypoglycemia as a new clinical feature that should be considered in ZC4H2 gene-mutation disorders.Conclusion
A Japanese family with AMC and ID caused by a novel ZC4H2 gene mutation was reported. Hypoglycemia should be considered one of the features in this disorder. 相似文献19.
20.
Pauline Marzin Cyril Mignot Nathalie Dorison Louis Dufour Dorothée Ville Anna Kaminska Eleni Panagiotakaki Anne-Sophie Dienpendaele Marie-José Penniello Marie-Christine Nougues Boris Keren Christel Depienne Caroline Nava Mathieu Milh Laurent Villard Christian Richelme Clotilde Rivier Sandra Whalen Diane Doummar 《Brain & development》2018,40(9):768-774