Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea
Background: Biallelically mutated MYO5B is associated with microvillus inclusion disease (MVID, MIM: 251850), cholestasis, or both. This study aims at validating the splicing alteration and clinical features of an intron variant for diagnosis.Case Presentation: A homozygous variant of MYO5B, NM_0010...
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| Format: | Article |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.872836/full |
| _version_ | 1818239446654386176 |
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| author | Yu Zheng Yuming Peng Shuju Zhang Hongmei Zhao Weijian Chen Yongjia Yang Zhengmao Hu Qiang Yin Yu Peng |
| author_facet | Yu Zheng Yuming Peng Shuju Zhang Hongmei Zhao Weijian Chen Yongjia Yang Zhengmao Hu Qiang Yin Yu Peng |
| author_sort | Yu Zheng |
| collection | DOAJ |
| description | Background: Biallelically mutated MYO5B is associated with microvillus inclusion disease (MVID, MIM: 251850), cholestasis, or both. This study aims at validating the splicing alteration and clinical features of an intron variant for diagnosis.Case Presentation: A homozygous variant of MYO5B, NM_001080467.2:c.2090+3A > T (NP_001073936.1:p.?) in intron 17, was identified in a patient suffering from chronic cholestasis and diarrhea. Functional validation showed that this variant caused 185 bp of intron retention in its mRNA and was predicted to present a premature translation termination site for myoVb (p.Arg697fs*47) in the head motor domain. In addition, bowel biopsy revealed decreased microvilli and local lesions of microvillus inclusion in the duodena of the patient. The patient was presented with neonatal cholestasis leading to cirrhosis, intractable diarrhea, cholelithiasis, hepatic cyst, corneal opacity, and failure to thrive.Conclusion: Our study demonstrated an intronic homozygous variant of MYO5B that affected an intron, subsequently altering splicing and leading to combined cholestasis and MVID. Our results further supported the underlying genotype–phenotype correlations and extended clinical practices toward its diagnosis and management. |
| first_indexed | 2024-12-12T12:57:41Z |
| format | Article |
| id | doaj.art-58c6b7a9f0154f55975c8c9e6e9cbc25 |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-12T12:57:41Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-58c6b7a9f0154f55975c8c9e6e9cbc252022-12-22T00:23:50ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-05-011310.3389/fgene.2022.872836872836Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and DiarrheaYu Zheng0Yuming Peng1Shuju Zhang2Hongmei Zhao3Weijian Chen4Yongjia Yang5Zhengmao Hu6Qiang Yin7Yu Peng8First Department of General Surgery & Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, ChinaFirst Department of General Surgery & Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, ChinaFirst Department of General Surgery & Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, ChinaDepartment of Gastroenterology and Nutrition, Hunan Children’s Hospital, Changsha, ChinaDepartment of Pathology, Hunan Children’s Hospital, Changsha, ChinaFirst Department of General Surgery & Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, ChinaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaFirst Department of General Surgery & Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, ChinaFirst Department of General Surgery & Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, ChinaBackground: Biallelically mutated MYO5B is associated with microvillus inclusion disease (MVID, MIM: 251850), cholestasis, or both. This study aims at validating the splicing alteration and clinical features of an intron variant for diagnosis.Case Presentation: A homozygous variant of MYO5B, NM_001080467.2:c.2090+3A > T (NP_001073936.1:p.?) in intron 17, was identified in a patient suffering from chronic cholestasis and diarrhea. Functional validation showed that this variant caused 185 bp of intron retention in its mRNA and was predicted to present a premature translation termination site for myoVb (p.Arg697fs*47) in the head motor domain. In addition, bowel biopsy revealed decreased microvilli and local lesions of microvillus inclusion in the duodena of the patient. The patient was presented with neonatal cholestasis leading to cirrhosis, intractable diarrhea, cholelithiasis, hepatic cyst, corneal opacity, and failure to thrive.Conclusion: Our study demonstrated an intronic homozygous variant of MYO5B that affected an intron, subsequently altering splicing and leading to combined cholestasis and MVID. Our results further supported the underlying genotype–phenotype correlations and extended clinical practices toward its diagnosis and management.https://www.frontiersin.org/articles/10.3389/fgene.2022.872836/fullmicrovillus inclusionRNA splicingintron retentionminigene assayMYO5Bdiarrhea |
| spellingShingle | Yu Zheng Yuming Peng Shuju Zhang Hongmei Zhao Weijian Chen Yongjia Yang Zhengmao Hu Qiang Yin Yu Peng Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea Frontiers in Genetics microvillus inclusion RNA splicing intron retention minigene assay MYO5B diarrhea |
| title | Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea |
| title_full | Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea |
| title_fullStr | Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea |
| title_full_unstemmed | Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea |
| title_short | Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea |
| title_sort | case report myo5b homozygous variant c 2090 3a t causes intron retention related to chronic cholestasis and diarrhea |
| topic | microvillus inclusion RNA splicing intron retention minigene assay MYO5B diarrhea |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.872836/full |
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