RESUMO
In 1997, a locus for benign familial infantile convulsions (BFIC) was mapped to chromosome 19q. Further data suggested that this locus is not involved in all families with BFIC. In the present report, we studied eight Italian families and mapped a novel BFIC locus within a 0.7-cM interval of chromosome 2q24, between markers D2S399 and D2S2330. A maximum multipoint HLOD score of 6.29 was obtained under the hypothesis of genetic heterogeneity. Furthermore, the clustering of chromosome 2q24-linked families in southern Italy may indicate a recent founder effect. In our series, 40% of the families are linked to neither chromosome 19q or 2q loci, suggesting that at least three loci are involved in BFIC. This finding is consistent with other autosomal dominant idiopathic epilepsies in which different genes were found to be implicated.
Assuntos
Cromossomos Humanos Par 2/genética , Epilepsia Neonatal Benigna/genética , Heterogeneidade Genética , Mapeamento Cromossômico , Cromossomos Humanos Par 19/genética , Feminino , Efeito Fundador , Genes Dominantes/genética , Marcadores Genéticos/genética , Humanos , Lactente , Recém-Nascido , Itália , Funções Verossimilhança , Escore Lod , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
Clinical features and results of the blood DNA analysis are reported of a child affected with a distinct phenotype of the late infantile form of neuronal ceroid-lipofuscinosis (LINCL). He was affected by microcephaly and hypotonia since the fourth month of life; acquisition of motor and language abilities was severely impaired, and a disorder of communication with stereotyped movements followed. By age four, he developed signs and symptoms of progressive myoclonic encephalopathy along with motor and cognitive deterioration. Extrapyramidal signs were associated with neuroradiological findings of marked atrophy of the caudate nucleus. Specific curvilinear bodies were observed in blood lymphocytes and skin biopsy. Homozygous, nonsense mutation in the CLN2 gene was found giving origin to an Arg208stop, which produces an early transcription termination with loss of translation of about 50% of the gene product. Any relationship between the severe clinical features of our patient and the homozygous mutation here reported must be investigated on a larger number of LINCL patients bearing the same mutation.
Assuntos
Núcleo Caudado/patologia , Códon sem Sentido/genética , Distonia/complicações , Expressão Gênica/genética , Lipofuscinoses Ceroides Neuronais/complicações , Lipofuscinoses Ceroides Neuronais/genética , Fatores de Transcrição/genética , Atrofia/complicações , Atrofia/patologia , Criança , Distonia/fisiopatologia , Potenciais Evocados Visuais/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Lipofuscinoses Ceroides Neuronais/diagnóstico , Tripeptidil-Peptidase 1RESUMO
PURPOSE: A locus for benign familial convulsions (BFICs) has been recently mapped on chromosome 19q12-13.1 by studying five families of Italian descent. The main goal of this study was to investigate the role of this locus in a set of seven newly identified families with at least three affected cases. METHODS: Five polymorphic microsatellite markers covering the BFIC locus on chromosome 19q have been typed, and parametric linkage analysis has been performed to analyze the segregation of the BFIC locus within our families. RESULTS: Cumulative 2-point lod scores and multipoint analysis showed no evidence of linkage between chromosome 19 markers and the BFIC phenotype. The analysis of family-specific 2-point lod scores and haplotypes, however, indicated the presence of linkage to chromosome 19q in a single family, suggesting genetic heterogeneity within our family sample. CONCLUSIONS: Our study demonstrates that the previously reported BFIC locus on chromosome 19q12-13.1 is not a major locus for BFICs. We suggest that genetic heterogeneity may have generated our discordant linkage findings, as it was reported in benign familial neonatal convulsions, a related idiopathic mendelian syndrome.
Assuntos
Cromossomos Humanos Par 19/genética , Família , Convulsões/genética , Mapeamento Cromossômico , Feminino , Ligação Genética , Marcadores Genéticos , Genótipo , Humanos , Itália/epidemiologia , Masculino , Convulsões/epidemiologiaRESUMO
OBJECTIVES: We report the analysis of scalp topography and dipole modeling of the rolandic spikes in 6 patients suffering of benign rolandic epilepsy of childhood with extremely high amplitude SEP by tapping stimulation of the finger of the hand. METHODS: EEG and BESA analysis were performed for both rolandic spontaneous interictal spikes and high amplitude scalp activity evoked by tapping and electrical stimulation of the first finger of the right hand. RESULTS: The evoked responses showed a morphology characterized by a rapid phase (spike) followed by a slow phase (slow wave). The spike presented an early small positive component followed by a main negative component. Similar morphology, dipole configuration and source localization were observed for both rolandic spikes and evoked high amplitude scalp responses. Dipole localization showed an overlap of spatial coordinates between rolandic and evoked spikes. CONCLUSIONS: These findings suggest that the extremely high amplitude SEPs could be evoked spikes which probably had the same cortical generators of the spontaneous rolandic spikes.
Assuntos
Mapeamento Encefálico , Epilepsia Rolândica/fisiopatologia , Potenciais Somatossensoriais Evocados , Criança , Estimulação Elétrica , Eletroencefalografia , Feminino , Humanos , Masculino , Estimulação Física , Couro CabeludoRESUMO
We performed a spike topography study and a functional magnetic resonance imaging (fMRI) in a female patient with benign rolandic epilepsy presenting single high-amplitude evoked spikes in response to somatosensory peripheral stimulation. The stimulus was delivered to the first finger of the right hand using a tendon hammer, which evoked a single spike followed by a slow wave, showing the maximal amplitude over the left central regions. fMRI showed that the contralateral sensory cortices (S1 and S2) and the motor cortex (M I) were activated during tapping stimulation. In 3 normal subjects, tapping stimulation produced no fMRI activation. This fMRI study documents a highly focal activation of sensorimotor areas related to subclinical evoked spikes in benign rolandic epilepsy.
Assuntos
Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/fisiopatologia , Imageamento por Ressonância Magnética , Estimulação Acústica , Criança , Eletroencefalografia , Potenciais Evocados Auditivos , Feminino , Humanos , Córtex Motor/fisiopatologia , Córtex Somatossensorial/fisiopatologiaRESUMO
We studied six patients suffering from benign rolandic epilepsy of childhood with central temporal spikes who presented so-called 'extreme somatosensory evoked potentials (SEPs)' following peripheral somatosensory stimulation. Stimuli were delivered to the fingers of one hand using both a triggered tendon hammer and low-intensity electrical stimulation. The electrical stimulation was delivered in sequences in different conditions (i.e. random order, 1, 3 and 10 Hz). Both tapping and electrical stimulation produced scalp evoked potentials in all subjects, characterized by a spike followed by a slow wave, similar in morphology and scalp distribution to the spontaneously occurring spikes. This paroxysmal activity was sensitive to stimulus rate; the number of evoked spikes was inversely related to the frequency of stimulation, being maximal at 1 Hz and disappearing at high frequencies (10 Hz). Spontaneous spikes disappeared during high-frequency stimulation but were present during low-frequency stimulation. Averaged SEPs at 3-Hz stimulation showed a late high-amplitude component, identical in morphology and distribution to the single evoked spike. We therefore conclude that, in these subjects, the so-called 'extreme SEPs' are evoked spikes and that evoked and spontaneous spikes share common cortical sensorimotor generators. The evidence that these generators can be influenced by afferent input provides important information regarding the functional mechanisms involved in modulating cortical excitability in benign rolandic epilepsy. Moreover, we suggest that peripheral electrical stimulation can be used as an additional activation test in this kind of epilepsy.