Open AccessMultimodal evaluation of an Italian family with a hereditary spastic paraplegia and POLR3A mutations
Author(s) -
Ruggiero Lucia,
Iovino Aniello,
Dubbioso Raffaele,
Cocozza Sirio,
Trovato Rosanna,
Aruta Francesco,
Pontillo Giuseppe,
Barghigiani Melissa,
Brunetti Arturo,
Santorelli Filippo Maria,
Manganelli Fiore,
Iodice Rosa
Publication year - 2020
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51221
Subject(s) - medicine , spastic , phenotype , paraplegia , hereditary spastic paraplegia , atrophy , gene , genetics , bioinformatics , physical medicine and rehabilitation , spinal cord , pathology , biology , cerebral palsy , psychiatry
Abstract We describe an Italian family with adult‐onset pure hereditary spastic paraplegia due to biallelic variants in POLR3A gene [c.1909 + 22G > A and c.3839dupT (p.M1280fs*20]. MRI showed a mild hyperintensity of superior cerebellar peduncles and cervical spinal cord atrophy. The neurophysiological metrics about intracortical excitability showed higher values of motor thresholds and a significant reduction of short interval intracortical inhibition (SICI) in the patient with a more severe phenotype. Our multimodal evaluation further expands the wide phenotypic spectrum associated with mutations in the POLR3A gene. An extensive genotype–phenotype correlation study is necessary to explain the role of the many new mutations on the function of protein.