BACKGROUND: Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC. METHODS: As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation. RESULTS: Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on (18)F-flurodeoxyglucose PET. CONCLUSIONS: Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark.
BACKGROUND:Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC. METHODS: As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation. RESULTS: Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on (18)F-flurodeoxyglucose PET. CONCLUSIONS: Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark.
Authors: Adeline Vanderver; Davide Tonduti; Sarah Auerbach; Johanna L Schmidt; Sumit Parikh; Gordon C Gowans; Kelly E Jackson; Pamela L Brock; Marc Patterson; Michelle Nehrebecky; Rena Godfrey; Wadih M Zein; William Gahl; Camilo Toro Journal: Mol Genet Metab Date: 2012-06-01 Impact factor: 4.797
Authors: Francisco Grandas; Manuel Desco; Francisco J Navas-Sánchez; Alberto Fernández-Pena; Daniel Martín de Blas; Yasser Alemán-Gómez; Luís Marcos-Vidal; Juan A Guzmán-de-Villoria; Pilar Fernández-García; Julia Romero; Irene Catalina; Laura Lillo; José L Muñoz-Blanco; Andrés Ordoñez-Ugalde; Beatriz Quintáns; Julio Pardo; María-Jesús Sobrido; Susanna Carmona Journal: J Neurol Date: 2021-01-28 Impact factor: 4.849
Authors: Felipe Franco da Graça; Thiago Junqueira Ribeiro de Rezende; Luiz Felipe Rocha Vasconcellos; José Luiz Pedroso; Orlando Graziani P Barsottini; Marcondes C França Journal: Front Neurol Date: 2019-01-16 Impact factor: 4.003