Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis

Complicated hereditary spastic paraplegias (HSP) are a heterogeneous group of HSP characterized by spasticity associated with a variable combination of neurologic and extra-neurologic signs and symptoms. Among them, HSP with thin corpus callosum and intellectual disability is a frequent subtype, often inherited as a recessive trait (ARHSP-TCC). Within this heterogeneous subgroup, SPG11 and SPG15 represent the most frequent subtypes. We analyzed the mutation frequency of three genes associated with early-onset forms of ARHSP with and without TCC, CYP2U1/SPG56, DDHD2/SPG54 and GBA2/SPG46, in a large population of selected complicated HSP patients by using a combined approach of traditional-based and amplicon-based high-throughput pooled-sequencing. Three families with mutations were identified, one for each of the genes analyzed. Novel homozygous mutations were identified in CYP2U1 (c.1A>C/p.Met1?) and in GBA2 (c.2048G>C/ p.Gly683Arg), while the homozygous mutation found in DDHD2 (c.1978G>C/p.Asp660His) had been previously reported in a compound heterozygous state. The phenotypes associated with the CYP2U1 and DDHD2 mutations overlap the SPG56 and the SPG54 subtypes, respectively, with few differences. By contrast, the GBA2 mutated patients show phenotypes combining typical features of both the SPG46 subtype and the recessive ataxia form, with marked intrafamilial variability thereby expanding the spectrum of clinical entities associated with GBA2 mutations. Overall, each of three genes analyzed shows a low mutation frequency in a general population of complicated HSP (<1% for either CYP2U1 or DDHD2 and approximately 2% for GBA2 ). These findings underline once again the genetic heterogeneity of ARHSP-TCC and the clinical overlap between complicated HSP and the recessive ataxia syndromes

The Effect of Frequency of Cerebral Palsy Treatment: A Matched-Pair Pilot Study

The feasibility and effectiveness of a year-long integrated rehabilitation program for young children (less than 6 years old) with cerebral palsy was evaluated, and efficacy of different treatment schedules was compared. A sample of 40 children (20 male; mean age, 3 years ±1.22) took part: 20 presented with tetraparesis, 12 with diparesis, and 8 with hemiparesis. Participants' motor abilities were classified according to the Gross Motor Function Measure classification system at baseline and after 1 year of treatment. For half of the participants, treatment consisted of continuous integrated intervention twice a week; for the other half, treatment was the 3i intervention (Intermittent, Intensive, Integrated), in which a month of intensive, twice-a-day treatment was followed by a continuous, twice-a-week phase, lasting 5 months. Overall, there was an improvement in gross motor function, with 37% of children improving and no children showing lowered function. Neither baseline general cognitive abilities nor age had a significant effect on the level of improvement, although initial gross motor function did. Children undergoing the intensive intermittent intervention showed the greatest motor function improvement. Results support the effectiveness of the integrated intervention and of periods of higher frequency intervention in young children

Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis

Complicated hereditary spastic paraplegias (HSP) are a heterogeneous group of HSP characterized by spasticity associated with a variable combination of neurologic and extra-neurologic signs and symptoms. Among them, HSP with thin corpus callosum and intellectual disability is a frequent subtype, often inherited as a recessive trait (ARHSP-TCC). Within this heterogeneous subgroup, SPG11 and SPG15 represent the most frequent subtypes. We analyzed the mutation frequency of three genes associated with early-onset forms of ARHSP with and without TCC, CYP2U1/SPG56, DDHD2/SPG54 and GBA2/SPG46, in a large population of selected complicated HSP patients by using a combined approach of traditional-based and amplicon-based high-throughput pooled-sequencing. Three families with mutations were identified, one for each of the genes analyzed. Novel homozygous mutations were identified in CYP2U1 (c.1A>C/p.Met1?) and in GBA2 (c.2048G>C/ p.Gly683Arg), while the homozygous mutation found in DDHD2 (c.1978G>C/p.Asp660His) had been previously reported in a compound heterozygous state. The phenotypes associated with the CYP2U1 and DDHD2 mutations overlap the SPG56 and the SPG54 subtypes, respectively, with few differences. By contrast, the GBA2 mutated patients show phenotypes combining typical features of both the SPG46 subtype and the recessive ataxia form, with marked intrafamilial variability thereby expanding the spectrum of clinical entities associated with GBA2 mutations. Overall, each of three genes analyzed shows a low mutation frequency in a general population of complicated HSP (<1% for either CYP2U1 or DDHD2 and approximately 2% for GBA2 ). These findings underline once again the genetic heterogeneity of ARHSP-TCC and the clinical overlap between complicated HSP and the recessive ataxia syndromes. © Springer-Verlag 2013

Correction to: Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review (Journal of Neurology, (2021), 10.1007/s00415-021-10792-3)

Unfortunately, the given name and family name of the first author was incorrectly tagged in the xml data, therefore it is abbreviated wrongly in Pubmed. The correct given name is Stefania and family name is Della Vecchia

Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review

none39nomixedVecchia S.D.; Tessa A.; Dosi C.; Baldacci J.; Pasquariello R.; Antenora A.; Astrea G.; Bassi M.T.; Battini R.; Casali C.; Cioffi E.; Conti G.; De Michele G.; Ferrari A.R.; Filla A.; Fiorillo C.; Fusco C.; Gallone S.; Germiniasi C.; Guerrini R.; Haggiag S.; Lopergolo D.; Martinuzzi A.; Melani F.; Mignarri A.; Panzeri E.; Pini A.; Pinto A.M.; Pochiero F.; Primiano G.; Procopio E.; Renieri A.; Romaniello R.; Sancricca C.; Servidei S.; Spagnoli C.; Ticci C.; Rubegni A.; Santorelli F.M.Vecchia, S. D.; Tessa, A.; Dosi, C.; Baldacci, J.; Pasquariello, R.; Antenora, A.; Astrea, G.; Bassi, M. T.; Battini, R.; Casali, C.; Cioffi, E.; Conti, G.; De Michele, G.; Ferrari, A. R.; Filla, A.; Fiorillo, C.; Fusco, C.; Gallone, S.; Germiniasi, C.; Guerrini, R.; Haggiag, S.; Lopergolo, D.; Martinuzzi, A.; Melani, F.; Mignarri, A.; Panzeri, E.; Pini, A.; Pinto, A. M.; Pochiero, F.; Primiano, G.; Procopio, E.; Renieri, A.; Romaniello, R.; Sancricca, C.; Servidei, S.; Spagnoli, C.; Ticci, C.; Rubegni, A.; Santorelli, F. M