title: Exome sequencing reveals novel SPG11 mutation in hereditary spastic paraplegia with complicated phenotypes.
abstract: We used a combined approach of whole-exome sequencing and candidate mutation validation to identify the disease-causing gene in a hereditary spastic paraplegia (HSP) patient with lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. HSP is a clinically and genetically heterogeneous neurodegenerative disorder characterized by degeneration of the corticospinal tract motor neurons and resulting in progressive lower limb spasticity, often with a complicated phenotype. We identified novel compound heterozygous mutations in the SPG11 gene in this patient as follows: a mutation in exon 32, c.6194C > G transition (p.S2056X) and a novel c.5121+1C > T splicing mutation. Our finding suggests that these novel compound heterozygous mutations in SPG11 are associated with HSP and lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. This study also demonstrates that exome sequencing is an efficient and rapid diagnostic tool for identifying the causes of some complex and genetically heterogeneous neurodegenerative diseases.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Yu-sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Cheng-yuan
authors.initials: CY
authors.lastname: Mao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Chang-he
authors.initials: CH
authors.lastname: Shi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Hui-xia
authors.initials: HX
authors.lastname: Niu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Hai-yang
authors.initials: HY
authors.lastname: Luo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Shang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors.forename: Shi-lei
authors.initials: SL
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China. Electronic address: xuyuming@zzu.edu.cn.
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Xu
mesh_terms: D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D059472:Exome / Q000235:genetics; D005091:Exons; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D011712:Pyramidal Tracts / Q000473:pathology; D012326:RNA Splicing / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology
chemical_list: D011506:Proteins; C520412:SPG11 protein, human
keywords: Ataxia; Exome sequencing; Hereditary spastic paraplegia; SPG11; Thin corpus callosum