Segmental maternal uniparental disomy of chromosome 7q in a patient with congenital chloride diarrhea. Issue 7 (4th June 2021)

• Record Type: Journal Article
• Authors: Lyu, Juanjuan; Huang, Zhuo; Chen, Hongbo; Sun, Xiaomei; Liu, Ying; Yuan, Chuanjie; Ye, Li; Yu, Dan; Wu, Jin
• Is Part Of: Journal of clinical laboratory analysis. Volume 35:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-04
• Subjects: Congenital chloride diarrhea -- mUPD -- Silver–Russell syndrome -- SLC26A3; Diagnosis, Laboratory -- Periodicals; Medical laboratory technology -- Periodicals; 616
• DOI: 10.1002/jcla.23862
• Languages: English
• ISSNs: 0887-8013

Abstract

Abstract: Background: The main symptoms of congenital chloride diarrhea (CCD) main symptoms are watery diarrhea, hypochloremia, and hypokalemic metabolic alkalosis. Silver–Russell syndrome (SRS) is a heterogeneous imprinting disorder characterized by severe intrauterine retardation, poor postnatal growth, and facial dysmorphism. Methods: Parent‐offspring trio whole‐exome sequencing was used to identify the causal variants. Sequencing reads were mapped to the reference of human genome version hg19. Sanger sequencing was performed as a confirmatory experiment. Results: The proband was a patient with SRS caused by maternal uniparental disomy 7. The CCD of the proband was caused by homozygous variant c.1515–1 (IVS13) G>A; both mutated alleles were inherited from her mother. Conclusion: We report the first clinical case of CCD and SRS occurring together. Patients with milder phenotypes may be difficult to diagnose in early stage, but close monitoring of potential complications is important for identification. Abstract : We report the first case of a female child presenting with CCD accompanied by maternal segmental UPD of chromosome 7 confirmed by molecular diagnosis. The proband was the only patient in the family and harbored a SLC26A3 variant (NM_000111.3:c.1515‐1G>A). The mother of the patient was heterozygous, whereas the father was wild‐type. After treatment of CCD, the patient still failed to thrive and had a typical dysmorphic feature. In the second genetic analysis, we found that at least 86.51 Mb of genome 7q11q36 (chr7: 65446986–151960086) was maternal uniparental disomy. We revised the diagnosis to CCD combined with SRS.