Guangyu Wang1, Xiaoqing Lv1, Ling Xu1, Rui Zhang2, Chuanzhu Yan1, Pengfei Lin3. 1. Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China. 2. Save Sight Institute, Central Clinical Medical School, University of Sydney, Sydney, NSW, 2000, Australia. 3. Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China. lpfsdu@foxmail.com.
Abstract
INTRODUCTION: Limb-girdle muscular dystrophy (LGMD) is a group of clinically heterogeneous muscle disorders commonly manifesting proximal limb girdle muscle weakness. There have been more than 30 subtypes of LGMD associated with causative genes and limb-girdle muscular dystrophy type 2J (LGMD2J) is caused by mutations in the TTN gene. METHODS: We report a Han Chinese family with LGMD2J. The proband and his sister both presented with weakness in the proximal lower limbs bilaterally. Muscle biopsy and genetic analysis were performed. RESULTS: Muscle biopsy of the proband showed dystrophic changes accompanied by rimmed vacuoles. Whole-exome sequencing identified novel compound heterozygous mutations in the TTN gene, including elongation (c.107962_107963delAT, p.I35988Sfs*26) and truncation (c.99125_99128dupACAG, p.S33043Rfs*9) variants in the proband and his sister. Both two variants have never been reported. Notably, we are the first to identify an elongation mutation in the TTN gene, broadening the genetic mutation spectrum of LGMD2J. DISCUSSION: Several variants in the last exon of the TTN gene have been reported, one of which was associated with LGMD2J. Besides, LGMD2J should be distinguished from other myopathies caused by mutations in the TTN gene. The pathogenesis of and specific curative methods for LGMD2J remain to be further elucidated.
INTRODUCTION: Limb-girdle muscular dystrophy (LGMD) is a group of clinically heterogeneous muscle disorders commonly manifesting proximal limb girdle muscle weakness. There have been more than 30 subtypes of LGMD associated with causative genes and limb-girdle muscular dystrophy type 2J (LGMD2J) is caused by mutations in the TTN gene. METHODS: We report a Han Chinese family with LGMD2J. The proband and his sister both presented with weakness in the proximal lower limbs bilaterally. Muscle biopsy and genetic analysis were performed. RESULTS: Muscle biopsy of the proband showed dystrophic changes accompanied by rimmed vacuoles. Whole-exome sequencing identified novel compound heterozygous mutations in the TTN gene, including elongation (c.107962_107963delAT, p.I35988Sfs*26) and truncation (c.99125_99128dupACAG, p.S33043Rfs*9) variants in the proband and his sister. Both two variants have never been reported. Notably, we are the first to identify an elongation mutation in the TTN gene, broadening the genetic mutation spectrum of LGMD2J. DISCUSSION: Several variants in the last exon of the TTN gene have been reported, one of which was associated with LGMD2J. Besides, LGMD2J should be distinguished from other myopathies caused by mutations in the TTN gene. The pathogenesis of and specific curative methods for LGMD2J remain to be further elucidated.
Authors: I Pénisson-Besnier; P Hackman; T Suominen; J Sarparanta; S Huovinen; I Richard-Crémieux; B Udd Journal: J Neurol Neurosurg Psychiatry Date: 2010-06-22 Impact factor: 10.154
Authors: Anni Evilä; Anna Vihola; Jaakko Sarparanta; Olayinka Raheem; Johanna Palmio; Satu Sandell; Bruno Eymard; Isabel Illa; Ricard Rojas-Garcia; Karolina Hankiewicz; Luis Negrão; Tuija Löppönen; Pekka Nokelainen; Mikko Kärppä; Sini Penttilä; Mark Screen; Tiina Suominen; Isabelle Richard; Peter Hackman; Bjarne Udd Journal: Ann Neurol Date: 2014-02-24 Impact factor: 10.422
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822