AUTHOR=Zheng Yu , Peng Yuming , Zhang Shuju , Zhao Hongmei , Chen Weijian , Yang Yongjia , Hu Zhengmao , Yin Qiang , Peng Yu 

TITLE=Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.872836

DOI=10.3389/fgene.2022.872836

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Biallelically mutated <italic>MYO5B</italic> 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.</p><p><bold>Case Presentation:</bold> A homozygous variant of <italic>MYO5B</italic>, NM_001080467.2:c.2090+3A &gt; 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.</p><p><bold>Conclusion:</bold> Our study demonstrated an intronic homozygous variant of <italic>MYO5B</italic> 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.</p>