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1.
Autosomal dominant partial epilepsy with auditory features: description of a new family 总被引:9,自引:5,他引:4
Michelucci R Passarelli D Pitzalis S Dal Corso G Tassinari CA Nobile C 《Epilepsia》2000,41(8):967-970
PURPOSE: To report the clinical and genetic study of a new family with autosomal dominant partial epilepsy with auditory features (ADPEAF). METHODS: All the living affected members underwent a full clinical, neurophysiological, and magnetic resonance imaging (MRI) study. Genetic analysis was performed by typing their DNA with seven microsatellite markers previously found to cosegregate with ADPEAF on chromosome 10q24. RESULTS: The three living affected members had a childhood onset of rare and drug-responsive tonic-clonic seizures constantly preceded by a humming sensation. Routine and sleep electroencephalograms revealed rare and inconstant focal abnormalities over both temporal regions. MRI detected atrophy with increased T2 signal in the subcortical lateral portion of the right temporal lobe in one case. Analysis of 10q24 polymorphic alleles showed the same haplotype in all three affected members but different alleles in unaffected individuals. CONCLUSIONS: ADPEAF is a distinct condition with homogeneous clinical features. Genetic findings are consistent with linkage of ADPEAF to chromosome 10q24. 相似文献
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Four new families with autosomal dominant partial epilepsy with auditory features: clinical description and linkage to chromosome 10q24 总被引:3,自引:2,他引:1
Winawer MR Martinelli Boneschi F Barker-Cummings C Lee JH Liu J Mekios C Gilliam TC Pedley TA Hauser WA Ottman R 《Epilepsia》2002,43(1):60-67
PURPOSE: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. METHODS: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. RESULTS: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (theta=0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. CONCLUSIONS: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway. 相似文献
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Roberto Michelucci Emanuela Dazzo Lilia Volpi Elena Pasini Patrizia Riguzzi Raffaella Minardi Anna Federica Marliani Maria Tappat Francesca Bisulli Carlo Alberto Tassinari Carlo Nobile 《Epileptic Disord》2020,22(4):443-448
Aims. Reelin mutations are responsible for a minority of families with autosomal dominant lateral temporal lobe epilepsy. Here, we report a novel nuclear family with distinct clinical and neuroradiological findings. Methods. We studied the proband and her mother by means of EEG, video‐EEG, 3T MRI, FDG‐PET and genetic testing. Results. Both patients had a focal drug‐resistant epilepsy with onset at the age of 16 and focal seizures with typical auditory features combined with fear, followed by loss of contact or evolving to bilateral tonic‐clonic seizures. The proband's ictal EEG showed clear left temporal seizure onset, and cerebral MRI revealed subtle left temporal changes (mild hypotrophy, slight blurring of the white and grey matter and hyperintensity) with corresponding left temporal mesial focal hypometabolism on FDG‐PET. Genetic testing identified a missense variant, c.6631C>T (p.Arg2211Cys), in reelin repeat #5 in both patients, which markedly affected the secretion of the protein. Conclusion. The data from this family support previous findings indicating that reelin mutations are a cause of autosomal dominant lateral temporal lobe epilepsy which has a clinical spectrum that may also encompass drug‐resistant epilepsy associated with mild MRI temporal changes. 相似文献
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Autosomal dominant lateral temporal epilepsy: clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families 总被引:11,自引:3,他引:8
Michelucci R Poza JJ Sofia V de Feo MR Binelli S Bisulli F Scudellaro E Simionati B Zimbello R D'Orsi G Passarelli D Avoni P Avanzini G Tinuper P Biondi R Valle G Mautner VF Stephani U Tassinari CA Moschonas NK Siebert R Lopez de Munain A Perez-Tur J Nobile C 《Epilepsia》2003,44(10):1289-1297
PURPSOE: To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE). METHODS: A personal and family history was obtained from each affected and unaffected member, along with a physical and neurologic examination. Routine and sleep EEGs, computed tomography (CT), or magnetic resonance imaging (MRI) were performed in almost all the patients. DNAs from family members were typed with several microsatellite markers localized on either side of LGI1 at 10q24 and screened for LGI1 mutations. RESULTS: The seven families included a total of 34 affected individuals (10 deceased). The age at onset ranged between 8 and 50 years (average, 22 years). Twenty-six patients had clear-cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Less frequent ictal symptoms were visual, psychic, or aphasic seizures, the latter occurring in isolation in one family. The attacks were rare and well controlled by antiepileptic drug treatment but recurred after drug discontinuation. Interictal EEGs were usually unrevealing. MRI or CT scans were negative. Analysis of LGI1/Epitempin exons failed to show mutations in three pedigrees. Linkage analysis strongly suggested exclusion of linkage in one of these families. We found two novel missense mutations, a T-->C substitution in exon 6 at position 598, and a T-->A transition in exon 8 at position 1295, the latter being detected in a family with aphasic seizures. CONCLUSIONS: Our data confirm the inclusion of aphasic seizures within the ADLTE clinical spectrum, suggest the existence of locus heterogeneity in ADLTE, and provide new familial cases with LGI1 missense mutations associated with the disease. 相似文献
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Auditory aura was the very important clinical character in familial temporal Lobe epilepsy. LGI1 was the main pathogenic gene. The inheritance mode of this disease was autosomal dominant. We describes the clinical characters and gene detection in 7 patients in a temporal lobe epilepsy family with auditory aura. All patients in this family were diagnosed as temporal lobe epilepsy and had the same mutation: the splice site mutation in No. 2 base of the intron after the first exon in gene LGI1, c.215+2T>A, which induced the abnormal expression of peptide protein after the No. 71 amino acid encoded by LGI1. Some of the antiepileptic drugs, such as carbamazepine, oxcarbazepine, could be effective. 相似文献
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Purpose: Generalized epilepsies are clinically and genetically heterogeneous syndromes. Idiopathic generalized epilepsy (IGE), which has a strong genetic background, is not associated with any additional clinical features, such as mental retardation (MR). Herein we report results of linkage analysis in a large family with autosomal dominant (AD) generalized epilepsy associated with MR. Methods: We identified a four‐generation kindred with several affected members with generalized epilepsy without any evidence for secondary causes. Electroencephalography (EEG) studies and magnetic resonance imaging (MRI) results were reviewed when available. We performed a genome‐wide linkage analysis. Key Findings: Fourteen individuals were classified as affected and an additional three were considered as nonpenetrant obligatory carriers. Thirteen affected individual had a history of generalized tonic–clonic seizures, and absence seizures were reported in nine affected individuals. There was no history of preceding febrile seizures. MR was present in nine affected individuals with epilepsy but the other affected individuals had normal intelligence. Neuroimaging did not reveal any structural abnormalities and EEG studies were consistent with IGE rather than symptomatic generalized epilepsy. Genetic analysis detected a group of markers with logarithmic (base 10) of odds (LOD) score >3 on chromosome 3p spanning a 5.5 Mbp region. Sequencing of several candidate genes, including dynein light chain‐A, golgin subfamily a4, leucine rich repeat (in FLII) interacting gene, serine/threonine‐protein kinase DCAMKL3 (doublecortin‐ like and CAM kinase‐like 3), laforin (EPM2A) interacting protein 1 (EPM2AIP1, programmed cell death 6 interacting protein, and CLIP‐associating protein 2 (cytoplasmic linker‐associated protein 2) (hOrbit2) genes did not identify the disease‐causing mutations. Significance: We report the identification of a genetic locus for generalized epilepsy associated with MR on chromosome 3p. Affected individuals have a form of genetic epilepsy with generalized seizures variably associated with MR. Despite the presence of MR in several affected patients, epilepsy phenotype was not fully consistent with symptomatic epilepsy and suggests a biologic continuum between symptomatic epilepsies and IGE. 相似文献
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Familial temporal lobe epilepsy with aphasic seizures and linkage to chromosome 10q22-q24 总被引:7,自引:1,他引:6
PURPOSE: To describe the phenotypic expression of a new family with familial lateral temporal lobe epilepsy with aphasic seizures, and to compare the findings with the clinical features of previously reported families linked to chromosome 10q22-q24. METHODS: Medical records were collected from 12 living affected members. The patients underwent a personal interview and a clinical neurologic examination. Results from interictal scalp EEGs and neuroimaging examinations were obtained. RESULTS: The cardinal ictal symptom was a brief sensory aphasia in eight of the patients. In four, this was accompanied by auditory symptoms, usually in the form of monotonous unformed sounds. Simple partial seizures with psychic or somatosensory seizures also were present. Visual ictal symptoms and complex partial seizures were absent. All patients had generalized tonic-clonic seizures. Magnetic resonance imaging (MRI) or computed tomography (CT) did not reveal morphologic correlates. Improvement with age seemed to occur in many patients. Significant linkage to chromosome 10q22-q24 was established by testing 17 polymorphic microsatellite markers. CONCLUSIONS: The epilepsy of this family appears to represent a variety of autosomal dominant lateral temporal lobe epilepsy. Aphasic seizures and a peculiar seizure-precipitating effect of the activation of speech (initiation or perception) may serve as markers for identifying further families with this phenotype. 相似文献
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Familial partial epilepsy with variable foci: clinical features and linkage to chromosome 22q12 总被引:4,自引:0,他引:4
Berkovic SF Serratosa JM Phillips HA Xiong L Andermann E Díaz-Otero F Gómez-Garre P Martín M Fernández-Bullido Y Andermann F Lopes-Cendes I Dubeau F Desbiens R Scheffer IE Wallace RH Mulley JC Pandolfo M 《Epilepsia》2004,45(9):1054-1060
BACKGROUND: Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant syndrome characterized by partial seizures originating from different brain regions in different family members in the absence of detectable structural abnormalities. A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French-Canadian families. METHODS: We describe the clinical features and performed a linkage analysis in a Spanish kindred and in a third French-Canadian family distantly related to the original pedigrees. RESULTS: Onset of seizures was typically in middle childhood, and attacks were usually easy to control. Seizure semiology varied among family members but was constant for each individual. In some, a pattern of nocturnal frontal lobe seizures led to consideration of the diagnosis of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The Spanish family was mapped to chromosome 22q (multipoint lod score, 3.4), and the new French-Canadian family had a multipoint lod score of 2.97 and shared the haplotype of the original French-Canadian families. CONCLUSIONS: Identification of the various forms of familial partial epilepsy is challenging, particularly in small families, in which insufficient individuals exist to identify a specific pattern. We provide clinical guidelines for this task, which will eventually be supplanted by specific molecular diagnosis. We confirmed linkage of FPEVF to chromosome 22q12 and redefined the region to a 5.2-Mb segment of DNA. 相似文献
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Hedera P Ma S Blair MA Taylor KA Hamati A Bradford Y Abou-Khalil B Haines JL 《Epilepsia》2006,47(10):1622-1628
PURPOSE: To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy. BACKGROUND: AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile seizures plus (GEFS+), is characterized by heterogeneous phenotypes including FS persisting beyond the usual age of remission or coexisting with afebrile seizures. Mutations in three subunits of sodium channel genes and one GABA(A)-receptor subunit gene have been identified in some GEFS+ pedigrees. Six genetic loci for FS have been reported so far, but the molecular basis of FS remains unknown. METHODS: We identified a five-generation family with 13 individuals affected by FS. Evidence was found for coexisting afebrile seizures in some affected individuals. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. After excluding previously identified loci associated with FS and epilepsy, a genome-wide search was performed. RESULTS: Two affected individuals reported only a single FS, whereas the other affected individuals had a history of repeated FS. Coexisting afebrile seizures developed in three individuals. The mode of inheritance was consistent with AD inheritance with an incomplete penetrance. Tight linkage to a group of markers on chromosome 21q22 was identified with flanking markers D21S1909 and D21S1444, and maximum 2-point lod score 3.35 for markers D21S1910 and D21S1894. We excluded four ion-channel genes within this 6.5-cM locus as a cause of FS and epilepsy in this family. CONCLUSIONS: We report a novel locus on chromosome 21q22 for AD FS. Identification of the gene causing epilepsy on chromosome 21q22 will advance our understanding of inherited epilepsy and FS, and possibly other types of epilepsies. 相似文献
10.
Baykan B Madia F Bebek N Gianotti S Güney AI Cine N Bianchi A Gökyiğit A Zara F 《Epilepsia》2004,45(5):479-487
PURPOSE: The study describes the clinical features of an inbred family from Turkey with three members affected by seizures and tests possible autosomal recessive (AR) inheritance by means of linkage analysis. METHODS: Personal and family history was obtained from each subject, and general physical, neurologic, and EEG examinations were performed. A set of 382 fluorescence-labeled markers was used for the initial genome-wide search. A further set of 83 markers was used to map the locus precisely and to exclude the remaining genome. RESULTS: Twelve individuals from three generations were examined. Two subjects were affected by idiopathic epilepsy, whereas, their brother experienced a single unprovoked generalized seizure. Two siblings affected by idiopathic epilepsy and their unaffected sister showed a photoparoxysmal response to photic stimulation. Nine family members reported migraine. The genome-wide search led to the identification of a unique homozygous, 15.1-cM region shared by subjects with seizures on chromosome 9q32-33 and providing a lod score of 2.9. This locus, however, was not associated with migraine in this pedigree. CONCLUSIONS: The study suggests that idiopathic epileptic traits with AR inheritance might be underestimated in the general population and that inbred pedigrees may represent powerful tools for the identification of AR genes. 相似文献
11.
José Morales‐Corraliza Pilar Gómez‐Garre Raúl Sanz Fernando Díaz‐Otero Eva Gutiérrez‐Delicado José M. Serratosa 《Epilepsia》2010,51(9):1910-1914
Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant form of partial epilepsy characterized by the presence of epileptic seizures originating from different cerebral lobes in different members of the same family. Linkage to chromosomes 22q12 and 2q36 has been reported, although only six families have been published. We studied a new FPEVF family including nine affected individuals. The phenotype in this family was similar to that previously described and consisted of nocturnal and daytime seizures with semiology suggesting a frontal lobe origin. A video‐EEG (electroencephalography) recording of the proband’s seizures is presented and revealed hyperkinetic seizures of frontal lobe origin preceded by left frontal spikes. We excluded linkage to chromosome 2q36 and found a suggestion of linkage to chromosome 22q12 with a lod score of 2.64 (θ = 0) for marker D22S689. 相似文献
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R. Wielaard M. Bornebroek R.A. Ophoff H.A.O. Winter-Warnars Ph. Scheltens R.R. Frants M.D. Ferrari J. Haan 《Clinical neurology and neurosurgery》1995,97(4):307-313
We describe a four-generation Dutch family suffering from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of twenty affected family members, ten are still alive. Age at onset of the strokes was between 29 and 52 years, with a mean of 41.8 years. This family has the typical clinical and radiological features of CADASIL (except for the occurrence of ischemic heart disease at a relatively young age in some subjects), and is linked to chromosome 19p13. This disease has so far been described in families from Finland, France, Germany, Italy, Japan, Spain and the United Kingdom, and there is a remarkable clinical and genetical homogeneity among all families reported, including this Dutch family. 相似文献
16.
Neelan Pillay Gavin C.A. Fabinyi Terry S. Myles Gregory J. Fitt Samuel F. Berkovic Graeme D. Jackson 《Epilepsia》2009,50(12):2611-2618
Purpose: Lesion‐negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging‐negative frontal or temporal lobe epilepsy. Methods: We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Results: Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T1‐ and T2‐weighted images with relative preservation of the gray–white matter boundary on T1‐weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure‐free (one has occasional auras only, follow‐up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. Discussion: In patients with lesion‐negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features. 相似文献
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Evidence of linkage to chromosome 5p13.2‐q11.1 in a large inbred family with genetic generalized epilepsy
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Demet Kinay Karen L. Oliver Erdem Tüzün John A. Damiano Canan Ulusoy Eva Andermann Michael S. Hildebrand Melanie Bahlo Samuel F. Berkovic 《Epilepsia》2018,59(8):e125-e129
The clinical genetics of genetic generalized epilepsy suggests complex inheritance; large pedigrees, with multiple affected individuals, are rare exceptions. We studied a large consanguineous family from Turkey where extensive electroclinical phenotyping revealed a familial phenotype most closely resembling juvenile myoclonic epilepsy. For a subject to be considered affected (n = 14), a diagnostic electroencephalogram was required. Seizure onset ranged between 6 and 19 years (mean = 12 years). Thirteen of 14 experienced myoclonic jerks; in 11, this was associated with eyelid blinking, and in 10 it was interspersed with absences. Generalized tonic–clonic seizures were seen in 11. One individual had generalized tonic–clonic seizures alone. Electroencephalograms demonstrated generalized polyspike and wave discharges that were not associated with photoparoxysmal response. Intellect was normal. Nineteen family members were subsequently chosen for nonparametric multipoint linkage analyses, which identified a 39.5 Mb region on chromosome 5 (P < 0.0001). Iterative analysis, including discovery of a subtly affected individual, narrowed the critical region to 15.4 Mb and possibly to 5.5 Mb. Homozygous versus heterozygous state of the refined 5p13.2‐q11.1 haplotype was not associated with phenotypic severity or onset age, suggesting that one versus two pathogenic variants may result in similar phenotypes. Whole exome sequencing (n = 3) failed to detect any rare, protein‐coding variants within the highly significant linkage region that includes HCN1 as a promising candidate. 相似文献
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Ettore Piro Rosaria Nardello Elena Gennaro Antonina Fontana Maurizio Taglialatela Giuseppe Donato Mangano Giovanni Corsello Salvatore Mangano 《Epileptic Disord》2019,21(1):87-91
Benign familial neonatal epilepsy (BFNE) is caused, in about 5% of families, by mutations in the KCNQ3 gene encoding voltage‐gated potassium channel subunits. Usually, newborns with BFNE show a normal neurological outcome, but recently, refractory seizures and/or developmental disability have been reported suggesting phenotype variability associated with KCNQ3‐related BFNE. Here, we describe a proband from a BFNE family carrying a novel variant in the KCNQ3 gene. Regarding the paucity of data in the literature, we describe the presented case with a view to further establishing: (1) a genotype/phenotype correlation in order to define a BFNE phenotype associated with favourable outcome; (2) an electroclinical pattern associated with BFNE based on video‐EEG recording; (3) appropriate first‐line AEDs; and (4) the duration of AED treatment. The presented case from Day 3 exhibited a cluster of ictal events, identified as epileptic seizures on Day 10 based on continuous video‐EEG polygraphy. The seizures were characterized by asymmetric tonic posturing, associated with a generalized decrease in EEG amplitude, and followed by bilateral asynchronous clonic movements associated with bicentral sharp‐wave discharges. The seizures were refractory to intravenous pyridoxine, whereas levetiracetam resulted in rapid total seizure control which has remained to date. This study demonstrates that the novel heterozygous KCNQ3 (c. 914A>T; p.Asp305Val) variant, affecting residues in the pore region, is associated with a specific electroclinical pattern and favourable neurodevelopmental outcome. [Published with video sequence on www.epilepticdisorders.com ] 相似文献
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An autopsy case of chromosome 16q22.1‐linked autosomal dominant cerebellar ataxia is reported. The patient was a 77‐year‐old man who died after a clinical course of about 19 years characterized by pure cerebellar ataxia. Main neuropathological findings included moderate loss of Purkinje cells, variegated degenerative features of the remaining Purkinje cells, finely fibrillary material surrounding the perikarya of Purkinje cells, and ubiquitin‐immunoreactive small dots in the molecular layer and cerebellar white matter. Neuritic hyperplasia surrounding the perikarya of Purkinje cells was also a prominent finding. Golgi impregnation study demonstrated poor dendritic arborization of some Purkinje cells. It is our assumption that the pathological processes leading to Purkinje cell death in this disorder are not singular because the intracellular functions of the protein coded by the mutant gene are manifold, and the multiplicity of the pathological processes is reflected in diverse cytomorphological changes seen in degenerating Purkinje cells. 相似文献