BACKGROUND: Seven loci for autosomal dominant hereditary spastic paraplegia (ADHSP) have been mapped. To date, two families of SPG12 (chromosome 19q13) have been analyzed; however, there is not enough clinical information on SPG12 to establish locus-phenotype correlations. METHODS: The authors studied 60 individuals from a large Italian family with ADHSP, in which 16 members in four generations were affected. They performed genetic linkage analysis with DNA markers from currently known ADHSP loci. After database searching, one candidate gene for SPG12 was analyzed by sequencing. RESULTS: The patients in this family showed an early onset and rapid progression of symptoms, resulting in severe disability, with a large proportion of affected members requiring use of a wheelchair. By age 16, most patients had sensory disturbance. Evidence for linkage to the SPG12 locus was obtained. Obligate recombination events observed in this family have narrowed the SPG12 locus from the 16.1 cM to 11.3 cM region between markers D19S416 and D19S412. In combination with previous genetic studies, the SPG12 locus was further narrowed to the 3.3 cM region between D19S416 and D19S220. A homologue of the AAA (ATPases associated with a variety of cellular activities) protein family, proteasome 26S subunit ATPase mapped near D19S220, was excluded by sequencing. CONCLUSIONS: This study refined the SPG12 region between D19S416 and D19S220 and revealed several clinical characteristics-early onset, rapid progression, and involvement of sensory disturbance-that may be unique to SPG12. Suggestive evidence of genetic anticipation was obtained, but should be confirmed in other SPG12 families.
BACKGROUND: Seven loci for autosomal dominant hereditary spastic paraplegia (ADHSP) have been mapped. To date, two families of SPG12 (chromosome 19q13) have been analyzed; however, there is not enough clinical information on SPG12 to establish locus-phenotype correlations. METHODS: The authors studied 60 individuals from a large Italian family with ADHSP, in which 16 members in four generations were affected. They performed genetic linkage analysis with DNA markers from currently known ADHSP loci. After database searching, one candidate gene for SPG12 was analyzed by sequencing. RESULTS: The patients in this family showed an early onset and rapid progression of symptoms, resulting in severe disability, with a large proportion of affected members requiring use of a wheelchair. By age 16, most patients had sensory disturbance. Evidence for linkage to the SPG12 locus was obtained. Obligate recombination events observed in this family have narrowed the SPG12 locus from the 16.1 cM to 11.3 cM region between markers D19S416 and D19S412. In combination with previous genetic studies, the SPG12 locus was further narrowed to the 3.3 cM region between D19S416 and D19S220. A homologue of the AAA (ATPases associated with a variety of cellular activities) protein family, proteasome 26S subunit ATPase mapped near D19S220, was excluded by sequencing. CONCLUSIONS: This study refined the SPG12 region between D19S416 and D19S220 and revealed several clinical characteristics-early onset, rapid progression, and involvement of sensory disturbance-that may be unique to SPG12. Suggestive evidence of genetic anticipation was obtained, but should be confirmed in other SPG12 families.
Authors: Paulo Victor Sgobbi de Souza; Wladimir Bocca Vieira de Rezende Pinto; Gabriel Novaes de Rezende Batistella; Thiago Bortholin; Acary Souza Bulle Oliveira Journal: Cerebellum Date: 2017-04 Impact factor: 3.847
Authors: Antonio Orlacchio; Carla Babalini; Antonella Borreca; Clarice Patrono; Roberto Massa; Sarenur Basaran; Renato P Munhoz; Ekaterina A Rogaeva; Peter H St George-Hyslop; Giorgio Bernardi; Toshitaka Kawarai Journal: Brain Date: 2010-01-28 Impact factor: 13.501
Authors: Gladys Montenegro; Adriana P Rebelo; James Connell; Rachel Allison; Carla Babalini; Michela D'Aloia; Pasqua Montieri; Rebecca Schüle; Hiroyuki Ishiura; Justin Price; Alleene Strickland; Michael A Gonzalez; Lisa Baumbach-Reardon; Tine Deconinck; Jia Huang; Giorgio Bernardi; Jeffery M Vance; Mark T Rogers; Shoji Tsuji; Peter De Jonghe; Margaret A Pericak-Vance; Ludger Schöls; Antonio Orlacchio; Evan Reid; Stephan Züchner Journal: J Clin Invest Date: 2012-01-09 Impact factor: 14.808