Compound heterozygous mutations of TYMP as underlying causes of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
| Autor: | Ki Wha Chung, Jung Hee Hwang, Byung Suk Yoon, Ha-Neul Jeong, Hye Jin Kim, Bum Chun Suh, Ji Hoon Park, Sun Wha Park, Byung-Ok Choi |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Heterozygote Cancer Research Mitochondrial DNA Molecular Sequence Data Biology Compound heterozygosity medicine.disease_cause DNA Mitochondrial Polymorphism Single Nucleotide Biochemistry Mitochondrial Encephalomyopathies Genetics medicine Humans Missense mutation Amino Acid Sequence Thymidine phosphorylase Allele Molecular Biology Alleles Thymidine Phosphorylase Mutation Base Sequence Point mutation Brain Heterozygote advantage Magnetic Resonance Imaging Pedigree Oncology Molecular Medicine Female Sequence Alignment |
| Zdroj: | Molecular Medicine Reports. 8:17-22 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2013.1479 |
| Popis: | Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive multiorgan disease, frequently associated with mutations in the thymidine phosphorylase (TYMP) gene. TYMP encodes thymidine phosphorylase (TP), which has an essential role in the nucleotide salvage pathway for mitochondrial DNA (mtDNA) replication. This study reports an MNGIE patient with novel compound heterozygous missense mutations (Thr151Pro and Leu270Pro) in TYMP. Each mutation was inherited from one parent. Neither mutation was found in the controls and the mutation sites were well conserved between different species. Neither large deletion nor causative point mutations were found in the mtDNA. The patient presented with MNGIE symptoms, including gastrointestinal discomfort, external ophthalmoplegia, pigmentary retinopathy and demyelinating type diffuse sensory motor polyneuropathy. The patient demonstrated an early-onset but mild phenotype, with 9.6% TP activity; therefore, patients with these compound heterozygous mutations may exhibit a mild phenotype with a variable onset age according to TP activity level. |
| Databáze: | OpenAIRE |
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