title: A novel thymidine phosphorylase mutation in a Chinese MNGIE patient.
abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with mitochondrial alterations. MNGIE is characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia, ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused by mutation of the TYMP gene. We studied the clinical and biochemical characteristics of a family with MNGIE. The proband was a 48-year-old male presenting with diarrhea and progressive weight loss. He also had ptosis and exhibited eyeball fixation. His blood and cerebrospinal fluid lactate levels were elevated. Magnetic resonance imaging of the brain revealed diffuse leukoencephalopathy. Ragged red fibers and cytochrome c oxidase-deficient fibers were apparent on muscle biopsy. His vision and ptosis deteriorated significantly during follow-up. Our clinical diagnosis of MNGIE was confirmed by TYMP gene analysis. We discovered a homozygous TYMP c.1193-1216 dup-GGGCGCTGCCGCTGGCGCTGGTGC mutation (a duplication). Some of the family members were heterozygous for the mutation but had no clinical features. We predicted the function of this mutation using PredictProtein and found that the secondary structure had changed in the region of the helix and strand, the transmembrane region, and the protein-protein binding sites. The family described herein exhibited biochemically, genetically, and functionally confirmed MNGIE syndrome.
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.|Department of Neurology, Chinese People's Liberation Army General Hospital, No. 28, Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Jian-Jian
authors.initials: JJ
authors.lastname: Fan
authors.affiliation: Department of Molecular Genetics, Guangzhou Kingmed Center for Clinical Laboratory Co., Ltd., Guangzhou, 510330, Guangdong, People's Republic of China.
authors.forename: Gui-Lin
authors.initials: GL
authors.lastname: Mo
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Gong
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Chai
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Hua-Xing
authors.initials: HX
authors.lastname: Meng
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China.
authors.forename: Chang-Xin
authors.initials: CX
authors.lastname: Li
authors.affiliation: Department of Neurology, ShanXi Medical Univeristy of First Hospital, No. 85, Jiefang South Road, Taiyuan, 030001, ShanXi, People's Republic of China. neuroguo@163.com.
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Guo
authors.affiliation: Department of Neurology, Chinese People's Liberation Army General Hospital, No. 28, Fuxing Road, Beijing, 100853, People's Republic of China. pucq30128@sina.com.
authors.forename: Chuan-Qiang
authors.initials: CQ
authors.lastname: Pu
mesh_terms: D044466:Asian People; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000503:physiopathology; D039141:Muscular Dystrophy, Oculopharyngeal; D009154:Mutation; D009886:Ophthalmoplegia / Q000151:congenital; D010375:Pedigree; D013939:Thymidine Phosphorylase / Q000235:genetics*; D028361:Mitochondrial Diseases
chemical_list: C543750:TYMP protein, human; D013939:Thymidine Phosphorylase
keywords: Mitochondrial neurogastrointestinal encephalomyopathy; TYMP; Thymidine phosphorylase