OBJECTIVE: To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings. DESIGN: Case reports and whole-exome DNA sequencing. SETTING: Neurogenetics clinic, Institute of Genetic Medicine, Newcastle upon Tyne, England. PATIENTS: Two adult siblings with a sensorimotor neuropathy, ataxia, and spasticity. MAIN OUTCOME MEASURES: Clinical, neurophysiological, imaging, and genetic data. RESULTS: Novel compound heterozygous frameshift mutations were detected in the SACS gene of both siblings, predicted to drastically truncate the sacsin protein. CONCLUSIONS: Whole-exome sequencing rapidly defined the genetic cause of the disorder, expanding the clinical phenotype associated with SACS mutations to include a severe sensorimotor neuropathy.
OBJECTIVE: To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings. DESIGN: Case reports and whole-exome DNA sequencing. SETTING: Neurogenetics clinic, Institute of Genetic Medicine, Newcastle upon Tyne, England. PATIENTS: Two adult siblings with a sensorimotor neuropathy, ataxia, and spasticity. MAIN OUTCOME MEASURES: Clinical, neurophysiological, imaging, and genetic data. RESULTS: Novel compound heterozygous frameshift mutations were detected in the SACS gene of both siblings, predicted to drastically truncate the sacsin protein. CONCLUSIONS: Whole-exome sequencing rapidly defined the genetic cause of the disorder, expanding the clinical phenotype associated with SACS mutations to include a severe sensorimotor neuropathy.
Authors: Katharina Vill; Wolfgang Müller-Felber; Dieter Gläser; Marius Kuhn; Veronika Teusch; Herbert Schreiber; Joachim Weis; Jörg Klepper; Anja Schirmacher; Astrid Blaschek; Manuela Wiessner; Tim M Strom; Bianca Dräger; Kristina Hofmeister-Kiltz; Moritz Tacke; Lucia Gerstl; Peter Young; Rita Horvath; Jan Senderek Journal: Hum Genet Date: 2018-11-21 Impact factor: 4.132
Authors: Helen R Griffin; Angela Pyle; Emma L Blakely; Charlotte L Alston; Jennifer Duff; Gavin Hudson; Rita Horvath; Ian J Wilson; Mauro Santibanez-Koref; Robert W Taylor; Patrick F Chinnery Journal: Genet Med Date: 2014-06-05 Impact factor: 8.822
Authors: John M Darlow; Rebecca Darlay; Mark G Dobson; Aisling Stewart; Pimphen Charoen; Jennifer Southgate; Simon C Baker; Yaobo Xu; Manuela Hunziker; Heather J Lambert; Andrew J Green; Mauro Santibanez-Koref; John A Sayer; Timothy H J Goodship; Prem Puri; Adrian S Woolf; Rajko B Kenda; David E Barton; Heather J Cordell Journal: Sci Rep Date: 2017-11-06 Impact factor: 4.379
Authors: Matthis Synofzik; Anne S Soehn; Janina Gburek-Augustat; Julia Schicks; Kathrin N Karle; Rebecca Schüle; Tobias B Haack; Martin Schöning; Saskia Biskup; Sabine Rudnik-Schöneborn; Jan Senderek; Karl-Titus Hoffmann; Patrick MacLeod; Johannes Schwarz; Benjamin Bender; Stefan Krüger; Friedmar Kreuz; Peter Bauer; Ludger Schöls Journal: Orphanet J Rare Dis Date: 2013-03-15 Impact factor: 4.123