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Una paraplejía espástica familiar japonesa asociada con una variante UBQLN2
Kazuki Watanabe1,2, Tatsuya Ema3, Kenji Shimizu4
1Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Journal of human genetics
|August 21, 2025
Resumen
Las variantes genéticas en UBQLN2 pueden causar enfermedades de las neuronas motoras como la esclerosis lateral amiotrófica (ELA). Este estudio identifica una nueva variante UBQLN2 que causa paraplejía espástica de inicio temprano (SPG) en una familia, lo que pone de relieve la necesidad de monitorear a largo plazo a los pacientes.
Área de la Ciencia:
- La genética
- Neurología
- Biología molecular
Sus antecedentes:
- El gen UBQLN2, ubicado en Xp11.21, codifica la ubiquilina 2, una proteína crucial para la homeostasis de las proteínas.
- Se sabe que las variantes de Missense en UBQLN2 causan esclerosis lateral amiotrófica (ELA), con asociaciones raras con esclerosis lateral primaria (EPL) y paraplejía espástica (SPG).
Objetivo del estudio:
- Informar de una nueva variante UBQLN2 identificada en una familia con paraplejía espástica (SPG).
- Caracterizar el fenotipo clínico y la progresión de la enfermedad asociados con esta variante UBQLN2.
- Revisar y comparar el fenotipo con las enfermedades de las neuronas motoras relacionadas con UBQLN2 reportadas anteriormente.
Principales métodos:
- Análisis genético para identificar la variante UBQLN2 (NM_013444.4: c.1442G>T, p.
- Evaluación clínica de los pacientes, incluida la edad de aparición, los síntomas (espasticidad de las extremidades inferiores, alteración de la marcha) y la progresión de la enfermedad.
- Revisión de la literatura de las variantes UBQLN2 y los fenotipos asociados de la enfermedad de las neuronas motoras.
Principales resultados:
- Cuatro pacientes varones de una misma familia presentaron una variante hemisigótica de UBQLN2.
- Los pacientes presentaron espasticidad de las extremidades inferiores con inicio en la infancia y trastornos progresivos de la marcha con una edad media de inicio de 11 años.
- La progresión de la enfermedad fue más lenta en comparación con los casos de ELA y EPL reportados anteriormente.
Conclusiones:
- La variante UBQLN2 identificada (p. Gly481Val) está asociada con una forma de paraplejía espástica (SPG) de inicio temprano y progresivo.
- La GSP relacionada con UBQLN2 puede presentarse antes y progresar más lentamente que la ELA o la EPL.
- Se recomienda una estrecha vigilancia de los pacientes con GSP relacionada con UBQLN2 debido a la posibilidad de progresión a fenotipos de ELA.
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