La neurodegeneración asociada a PLA2G6 (PLAN) y la paraplejía espástica hereditaria (HSP) son dos grupos de enfermedades neurodegenerativas heterogéneas. En este estudio, informamos mutaciones del gen PLA2G6 en tres familias de Turquía, Marruecos y Rumania. Dos hermanos turcos afectados que presentan HSP añaden la enfermedad a los fenotipos de PLAN. Eran homocigotos para la variante PLA2G6 missense c.2239C>T, p.Arg747Trp y las edades de inicio fueron 9 y 21 años. El parkinsonismo, la distonía o el deterioro cognitivo no fueron elementos clínicos en estos pacientes a diferencia de los casos reportados previamente. Con la misma variante, sin embargo, la acumulación de hierro fue evidente en su resonancia magnética craneal. El paciente marroquí era homocigoto para una nueva variante sin sentido c.1786C>T, p.Leu596Phe y el paciente rumano tenía dos mutaciones nuevas; c.1898C>T, p.Ala633Val y c.1765_1768del, p.Ser589ThrfsTer76. Ambos pacientes se ajustaron mejor al PLAN de inicio en la infancia con una edad de inicio a los cuatro y siete años, respectivamente. Curiosamente, todas las mutaciones identificadas afectaban al dominio fosfolipasa similar a la patatina altamente conservado de la proteína PLA2G6.
PLA2G6 MUTATIONS ASSOCIATED WITH A CONTINUOUS CLINICAL SPECTRUM FROM NEUROAXONAL DYSTROPHY TO HEREDITARY SPASTIC PARAPLEGIA
PLA2G6-associated neurodegeneration (PLAN) and hereditary spastic paraplegia (HSP) are two groups of heterogeneous neurodegenerative diseases. In this study, we report PLA2G6 gene mutations in three families from Turkey, Morocco, and Romania. Two affected Turkish siblings presenting HSP adds the disease to PLAN phenotypes. They were homozygous for the PLA2G6 missense c.2239C>T, p.Arg747Trp variant and the ages of onset were 9 and 21. Parkinsonism, dystonia or cognitive decline were not the clinical elements in these patients contrary to the cases that has been previously reported with the same variant, however, iron accumulation was evident in their cranial MRI. The Moroccan patient was homozygous for a novel missense c.1786C>T, p.Leu596Phe variant and the Romanian patient had two novel mutations; c.1898C>T, p.Ala633Val and c.1765_1768del, p.Ser589ThrfsTer76. Both of these patients conformed better to childhood onset PLAN with the age of onset at four and seven years, respectively. Interestingly, all identified mutations were affecting the highly conserved patatin-like phospholipase domain of the PLA2G6 protein.
