RESUMEN
We report on a family with an autosomal dominant cerebellar ataxia in which we identified a novel mutation in exon 5 of the PRKCG/SCA14 gene that results in a Val138Glu substitution in the encoded protein PKCgamma. While most affected subjects displayed a late-onset uncomplicated form of spinocerebellar ataxia with occasional mild extrapyramidal features (such as postural tremor), one patient presented with a very mild nonprogressive ataxia since the age of 3 years and predominant multifocal myoclonus.
Asunto(s)
Análisis Mutacional de ADN , Isoenzimas/genética , Fenotipo , Proteína Quinasa C/genética , Ataxias Espinocerebelosas/genética , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos/genética , Atrofia , Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/genética , Cerebelo/patología , Exones , Femenino , Ácido Glutámico/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación Missense , Mioclonía/diagnóstico , Mioclonía/genética , Países Bajos , Linaje , Ataxias Espinocerebelosas/diagnóstico , Temblor/diagnóstico , Temblor/genética , Valina/genéticaRESUMEN
Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited disorder. Complete deficiency of HPRT activity is phenotypically expressed as the devastating Lesch-Nyhan syndrome. Partial HPRT deficiency usually causes hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18-year follow-up of a 5-year old boy with partial HPRT deficiency and report a novel mutation in his HPRT gene. He presented with overproduction of uric acid and passage of uric acid renal stones, and without gout or neurological and behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary alkalization, and a low-purine diet was started. No subsequent nephrolithiasis has occurred. After 18-year of this therapy his physical and neuropsychological status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of initial renal impairment in our patient is uric and/or xanthine crystalluria. A missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the patient's HPRT gene was identified and the mother was the carrier of the mutation. As far as we are aware, the identified mutation has not previously been reported. We named the mutant HPRT Maribor.