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Cited by 10Mitochondrial Function and PathologyMetabolism and Genetic DisordersHereditary Neurological Disorders

Clinical and molecular characterization of a patient with mitochondrial Neurogastrointestinal Encephalomyopathy

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Habibzadeh, Parham, Silawi, Mohammad, Dastsooz, Hassan, Bahramjahan, Shima, Ezzatzadegan Jahromi, Shahrokh, Ostovan, Vahid Reza, Yavarian, Majid, Mofatteh, Mohammad +1 more·2020·BMC Gastroenterology
DOI 10.1186/s12876-020-01280-5PMC PMC7206720
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Abstract

Background: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by mutations in TYMP gene, encoding nuclear thymidine phosphorylase (TP). MNGIE mainly presents with gastrointestinal symptoms and is mostly misdiagnosed in many patients as malabsorption syndrome, inflammatory bowel disease, anorexia nervosa, and intestinal pseudo-obstruction. Up to date, more than 80 pathogenic and likely pathogenic mutations associated with the disease have been reported in patients from a wide range of ethnicities. The objective of this study was to investigate the underlying genetic abnormalities in a 25-year-old woman affected with MNGIE. Case presentation: The patient was a 25-year-old female referred to our center with the chief complaint of severe abdominal pain and diarrhea for 2 years that had worsened from 2 months prior to admission. The clinical and para-clinical findings were in favor of mitochondrial neurogastrointestinal encephalomyopathy syndrome. Subsequent genetic studies revealed a novel, private, homozygous nonsense mutation in TYMP gene (c. 1013 C > A, p.S338X). Sanger sequencing confirmed the new mutation in the proband. Multiple sequence alignment showed high conservation of amino acids of this protein across different species. Conclusion: The detected new nonsense mutation in the TYMP gene would be very important for genetic counseling and subsequent early diagnosis and initiation of proper therapy. This novel pathogenic variant would help us establish future genotype-phenotype correlations and identify different pathways related to this disorder.

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  • Disease-modifying strategies such as allogeneic stem cell transplantation, liver transplantation, and experimental gene therapy approaches aim to correct thymidine phosphorylase deficiency and may alter trajectory in selected patients with MNGIE.

    “Case series and mechanistic studies highlight the importance of early recognition, as disease-modifying strategies such as allogeneic stem cell transplantation, liver transplantation, and experimental gene therapy approaches aim to correct thymidine phosphorylase deficiency and may alter trajectory in selected patients (D’Angelo et al., 2020; Filosto et al., 2012; Habibzadeh et al., 2020; Yadak et”

    From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as Habibzadeh et al., 2020

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References 42 · Cited by 10

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Authors
Habibzadeh, P., Silawi, M., Dastsooz, H., Bahramjahan, S., Ezzatzadegan Jahromi, S., Ostovan, V. R., Yavarian, M., Mofatteh, M., & Faghihi, M. A.
Affiliations
  • Shiraz University of Medical Sciences (IR)
  • Shiraz University (IR)
  • University of Oxford (GB)
  • University of Miami (US)
Corresponding author
Faghihi, Mohammad Ali
ORCID
Venue
BMC Gastroenterology
Publisher
Springer Science and Business Media LLC
Published
2020-05-08
Volume
20
Issue
1
Pages
142-142
ISSN
1471-230X (ISSN-L)
DOI
10.1186/s12876-020-01280-5
PMC
PMC7206720
OpenAlex
W3022092791
Cited by
10
References
42
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 4 · 2021: 3
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Gastroenterology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (US NIH NINDS R01NS081208-01A1)
  • National Institute for Medical Research Development (940714)
  • Persian BayanGene Research Grant (2018-01-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
mitochondrial neurogastrointestinal encephalomyopathy, thymidine phosphorylase, novel nonsense mutation, homozygous mutation, gastrointestinal symptoms, diarrhea, abdominal pain, misdiagnosis, genotype-phenotype correlation, genetic counseling, autosomal recessive disorder
MeSH terms
Adult, Diarrhea, Female, Gastrointestinal Diseases, Humans, Thymidine Phosphorylase, Abdominal Pain, Mitochondrial Encephalomyopathies, Codon, Nonsense

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