RESUMEN
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder first described among French Canadians in Quebec. To date, 24 mutations have been reported in the SACS gene of ARSACS patients. The authors report a clinical and genetic analysis of a Japanese family with ARSACS with novel compound heterozygous mutations in the SACS gene (N161fsX175, L802P). The phenotype is similar to that of previously reported ARSACS patients.
Asunto(s)
Ataxia Cerebelosa/genética , Trastornos de los Cromosomas/genética , Genes Recesivos/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Choque Térmico/genética , Mutación/genética , Atrofia/genética , Atrofia/patología , Atrofia/fisiopatología , Secuencia de Bases/genética , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Cerebelo/patología , Cerebelo/fisiopatología , Cromosomas Humanos Par 13/genética , Análisis Mutacional de ADN , Exones/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/etnología , Heterocigoto , Humanos , Japón , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Espasticidad Muscular/genética , Espasticidad Muscular/patología , Espasticidad Muscular/fisiopatología , Linaje , Fenotipo , Médula Espinal/patología , Médula Espinal/fisiopatologíaRESUMEN
To provide a genetic survey of hereditary ataxia, we performed PCR screening of SCA1, SCA2, MJD1 (SCA 3), SCA6, DRPLA, with 71 patients in 61 families living in Akita prefecture (1,205,571 population in 1997) in Japan. Of 71 patients in 61 families, 18 MJD1, 14 SCA6, 5 DRPLA, 1 SCA1 and 1 SCA2 patients were detected. Eighty percent of autosomal dominant inherited spinocerebellar degeneration (AD-SCD) including 7 spoladic patients genetically diagnosed as AD-SCD was MJD1 (45.7%) and SCA6 (34.3%). These suggest the prevalence rate of hereditary ataxias in Akita prefecture; 1.5 and 1.2/100,000 of MJD1 and SCA6, respectively. Only one patient of SCA1 was detected, which was frequently reported in Hokkaido and Tohoku area in Japan.
Asunto(s)
Pruebas Genéticas , Degeneraciones Espinocerebelosas/genética , Humanos , Japón/epidemiología , Reacción en Cadena de la Polimerasa , Prevalencia , Degeneraciones Espinocerebelosas/diagnóstico , Degeneraciones Espinocerebelosas/epidemiología , Expansión de Repetición de TrinucleótidoRESUMEN
We analyzed muscle area in CT and muscle pathology in a patient with isolated ACTH deficiency who started with the difficulty of elevation of both arms. Cortisol treatment resulted in full recovery from severe muscle atrophy and contracture of major joints. Change of volume of major muscles in arm, thigh and calf was followed. Major muscles were identified in CT and the area of each muscle was calculated with computer assistance. The increase of total muscle area in sequential 3 times in CT was up to 74% after prednisolone treatment. This indicates that the deficiency of cortisol resulted in 42% reduction of muscle volume. This also suggests that reduction of muscle volume induces the limitation of range of motion of shoulder joint. ATPase of muscle biopsy revealed the influence on fiber type proportion; type 1 : type 2A : type 2B = 29.6 : 6.0 : 64.4% and 35.7 : 17.6 : 46.7% in pre-treatment and post-treatment of cortisol, respectively. Mean diameters of muscle fibers in type 1, type 2A and type 2B was 41.8, 41.8, 39.1 microns and 46.2, 44.0, 37.2 microns in pre-treatment and post-treatment of cortisol, respectively. These suggest that deficiency of glucocorticoid introduces the reduction of the activity of the motor neurons innervating type 1 and type 2A muscle fibers.
Asunto(s)
Hormona Adrenocorticotrópica/deficiencia , Músculos/patología , Atrofia , Humanos , Hidrocortisona/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
Peripheral myelin protein 22 (PMP22), a membrane glycoprotein, plays a significant role in the formation and/or maintenance of compact myelin in the peripheral nervous system. We studied two pedigrees with Dejerine-Sottas disease and identified two novel mutations in the PMP22 gene: one a 2-bp deletional mutation at nucleotide positions 426 and 427 of exon 4 (this is predicted to alter the reading frame at leucine 80 and thus to lead to frame-shifted translation), and the other a guanine to thymine substitution at nucleotide position 636 leading to a cysteine substitution for glycine 150. Both mutations were located in the putative transmembrane domains reported in many cases of Charcot-Marie-Tooth neuropathy, Dejerine-Sottas disease, and hereditary neuropathy with liability to pressure palsies. The results suggest an important role for the putative transmembrane domains of PMP22 in its function.
Asunto(s)
Neuropatía Hereditaria Motora y Sensorial/genética , Proteínas de la Mielina/genética , Mutación Puntual/genética , Eliminación de Secuencia/genética , Adulto , Membrana Celular , ADN/sangre , Análisis Mutacional de ADN , Femenino , Heterogeneidad Genética , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo Conformacional Retorcido-Simple , ARN Mensajero/genética , Mapeo RestrictivoRESUMEN
To investigate the clinical range of spinocerebellar ataxia type 6 (SCA6), we screened CAG repeat expansion in the voltage-dependent alpha 1A calcium channel gene (CACNL1A4) in 71 ataxic patients in 60 families; 54 patients in 43 families with hereditary ataxia and 17 sporadic patients. Thirteen patients with SCA6 were detected to have elongated CAG in CACNL1A4. Of these, 7 patients had been diagnosed as having hereditary cerebellar cortical atrophy, and 6 patients had been found to have sporadic occurrence. One patient showed distinct pontine atrophy with prominent horizontal or oblique gaze nystagmus which is an unusual feature in sporadic olivopontocerebellar atrophy. For the efficient screening of SCA6, we would propose testing CAG repeat expansion in CACNL1A4, in patients with one of two markers: (1) horizontal or oblique gaze nystagmus without other eye movement disorders, (2) pure cerebellar atrophy, even if occurrence is sporadic. We should note that the pontine atrophy could also be caused by CAG repeat expansion in CACNL1A4.