Gholizad-Kolveiri, S. and Hooman, N. and Alizadeh, R. and Hoseini, R. and Otukesh, H. and Talebi, S. and Akouchekian, M. (2020) Whole exome sequencing revealed a novel homozygous variant in the DGKE catalytic domain: A case report of familial hemolytic uremic syndrome. BMC Medical Genetics, 21 (1).
Full text not available from this repository.Abstract
Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia caused by small vessel thrombosis, thrombocytopenia, and renal failure. The common cause of aHUS is a dysregulation in the alternative complement pathway. Mutations in none complement genes such as diacylglycerol kinase epsilon (DGKE) can also result in this syndrome. Case presentation: Here, we report on a 19-year-old female with the clinical diagnosis of aHUS, who has unaffected consanguineous parents and an older sibling who was deceased from aHUS when she was seven months old. We performed whole exome sequencing (WES) followed by evaluation of detected variants for functional significance, using several online prediction tools. Next, in order to confirm the detected pathogenic variant in proband and segregation analysis in her family, Sanger sequencing was done. The novel variant was analyzed in terms of its impact on the protein 3-dimensional structure by computational structural modeling. The results revealed that the proband carried a novel homozygous missense variant in DGKE located in exon 6 of the gene (NM003647.3, c.942C > G p.Asn314Lys), and in silico analysis anticipated it as damaging. Protein computational study confirmed the influence of potential pathogenic variant on structural stability and protein function. Conclusion: We suggest that some variations in the catalytic domain of DGKE like p.Asn314Lys which can cause alterations in secondary and 3-D structure of protein, might lead to aHUS. © 2020 The Author(s).
| Item Type: | Article |
|---|---|
| Additional Information: | cited By 0 |
| Uncontrolled Keywords: | creatinine; diacylglycerol kinase; diacylglycerol kinase epsilon; unclassified drug; von Willebrand factor cleaving proteinase; diacylglycerol kinase; diacylglycerol kinase epsilon, human, adult; amino acid sequence; amino acid substitution; anuria; Article; case report; chromosome 17; chronic kidney failure; clinical article; creatinine blood level; DGKE gene; enzyme activity; exon; female; gene; gene frequency; gene identification; gene location; gene segregation; genetic association; hematuria; hemolytic uremic syndrome; heterozygosity; histopathology; homozygosity; human; human tissue; hypertension; indel mutation; Iranian (citizen); laboratory test; missense mutation; pathogenesis; protein folding; protein structure; proteinuria; Sanger sequencing; segregation analysis; sequence alignment; single nucleotide polymorphism; thrombotic thrombocytopenic purpura; urea nitrogen blood level; whole exome sequencing; young adult; chemistry; consanguinity; enzyme active site; genetics; hemolytic uremic syndrome; homozygote; male; missense mutation; pedigree; procedures; whole exome sequencing, Atypical Hemolytic Uremic Syndrome; Catalytic Domain; Consanguinity; Diacylglycerol Kinase; Female; Homozygote; Humans; Male; Mutation, Missense; Pedigree; Whole Exome Sequencing; Young Adult |
| Subjects: | WJ Urogenital System |
| Depositing User: | eprints admin |
| Date Deposited: | 25 May 2021 08:00 |
| Last Modified: | 25 May 2021 08:00 |
| URI: | http://eprints.iums.ac.ir/id/eprint/34237 |
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