OBJECTIVE: To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed "Asidan") caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene. METHODS: We investigated the clinical, genetic, and neuropathologic characteristics of 18 patients with SCA36. We performed histologic evaluation of a muscle biopsy specimen from 1 patient with SCA36, and neuropathologic evaluation of an autopsied brain from another patient with SCA36. RESULTS: The (GGCCTG)n expansion was found in 18 ataxic patients from 9 families. The age at onset of ataxia was 53.1 ± 3.4 years, with the most frequent symptoms being truncal ataxia (100% of patients), ataxic dysarthria (100%), limb ataxia (93%), and hyperreflexia (79%). Tongue fasciculation and subsequent atrophy were found in 71% of cases, particularly in those of long duration. Skeletal muscle fasciculation and atrophy of the limbs and trunk were found in 57% of cases. Lower motor involvement was confirmed by EMG and muscle biopsy. The neuropathologic study revealed significant cerebellar Purkinje cell degeneration with obvious loss of lower motor neurons. Immunohistochemical analysis showed that NOP56 was localized to the nuclei of various neurons. Cytoplasmic or intranuclear inclusion staining of NOP56, TDP-43, and ataxin-2 was not observed in the remaining neurons. CONCLUSIONS: This is the first description of the unique clinical features of SCA36, a relatively pure cerebellar ataxia with progressive motor neuron involvement. Thus, SCA36 is a disease that stands at the crossroads of SCA and motor neuron disease.
OBJECTIVE: To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed "Asidan") caused by a hexanucleotideGGCCTG repeat expansion in intron 1 of the NOP56 gene. METHODS: We investigated the clinical, genetic, and neuropathologic characteristics of 18 patients with SCA36. We performed histologic evaluation of a muscle biopsy specimen from 1 patient with SCA36, and neuropathologic evaluation of an autopsied brain from another patient with SCA36. RESULTS: The (GGCCTG)n expansion was found in 18 ataxicpatients from 9 families. The age at onset of ataxia was 53.1 ± 3.4 years, with the most frequent symptoms being truncal ataxia (100% of patients), ataxic dysarthria (100%), limb ataxia (93%), and hyperreflexia (79%). Tongue fasciculation and subsequent atrophy were found in 71% of cases, particularly in those of long duration. Skeletal muscle fasciculation and atrophy of the limbs and trunk were found in 57% of cases. Lower motor involvement was confirmed by EMG and muscle biopsy. The neuropathologic study revealed significant cerebellar Purkinje cell degeneration with obvious loss of lower motor neurons. Immunohistochemical analysis showed that NOP56 was localized to the nuclei of various neurons. Cytoplasmic or intranuclear inclusion staining of NOP56, TDP-43, and ataxin-2 was not observed in the remaining neurons. CONCLUSIONS: This is the first description of the unique clinical features of SCA36, a relatively pure cerebellar ataxia with progressive motor neuron involvement. Thus, SCA36 is a disease that stands at the crossroads of SCA and motor neuron disease.
Authors: Zachary T McEachin; Tania F Gendron; Nisha Raj; María García-Murias; Anwesha Banerjee; Ryan H Purcell; Patricia J Ward; Tiffany W Todd; Megan E Merritt-Garza; Karen Jansen-West; Chadwick M Hales; Tania García-Sobrino; Beatriz Quintáns; Christopher J Holler; Georgia Taylor; Beatriz San Millán; Susana Teijeira; Toru Yamashita; Ryuichi Ohkubo; Nicholas M Boulis; Chongchong Xu; Zhexing Wen; Nathalie Streichenberger; Brent L Fogel; Thomas Kukar; Koji Abe; Dennis W Dickson; Manuel Arias; Jonathan D Glass; Jie Jiang; Malú G Tansey; María-Jesús Sobrido; Leonard Petrucelli; Wilfried Rossoll; Gary J Bassell Journal: Neuron Date: 2020-05-05 Impact factor: 17.173
Authors: Marco Antonio Araujo Leite; Marco Orsini; Marcos R G de Freitas; João Santos Pereira; Fábio Henrique Porto Gobbi; Victor Hugo Bastos; Dionis de Castro Machado; Sergio Machado; Oscar Arrias-Carrion; Jano Alves de Souza; Acary Bulle Oliveira Journal: Neurol Int Date: 2014-08-08
Authors: Tiffany W Todd; Zachary T McEachin; Jeannie Chew; Alexander R Burch; Karen Jansen-West; Jimei Tong; Mei Yue; Yuping Song; Monica Castanedes-Casey; Aishe Kurti; Judith H Dunmore; John D Fryer; Yong-Jie Zhang; Beatriz San Millan; Susana Teijeira Bautista; Manuel Arias; Dennis Dickson; Tania F Gendron; María-Jesús Sobrido; Matthew D Disney; Gary J Bassell; Wilfried Rossoll; Leonard Petrucelli Journal: Cell Rep Date: 2020-05-05 Impact factor: 9.995