Abstract: PO1664
A Case with Somatic and Germline Mosaicism in COL4A5 Detected by Multiplex Ligation-Dependent Probe Amplification in X-Linked Alport Syndrome
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Aoto, Yuya, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Nakanishi, Koichi, Department of Child Health and Welfare (Pediatrics), Faculty of Medicine, University of the Ryukyu, Nishihara, Japan
- Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Horinouchi, Tomoko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Yamamura, Tomohiko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Ishiko, Shinya, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Sakakibara, Nana, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Shima, Yuko, Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
- Iijima, Kazumoto, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
- Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
Group or Team Name
- Department of Pediatrics, Kobe University Graduate School of Medicine
Introduction
X-linked Alport syndrome (XLAS) is a progressive hereditary kidney disease caused by mutations in COL4A5 gene encoding the type IV collagen α5 chain. To date, 11 cases with somatic mosaicism in COL4A5 have been reported; however, all of them involved single-nucleotide variations (SNVs). Copy number variations (CNVs) in COL4A5 have also been reported, and pathogenic CNVs are relatively rare. Here, we report a female XLAS patient with somatic mosaicism identified by CNVs in COL4A5.
Case Description
The case was a 35-year-old female, the mother of the proband, whose only clinical symptom was hematuria. The proband was the son of this patient. His hematuria was detected at 3 months of age, and gross hematuria was occasionally exhibited. At the age of 2, proteinuria was persisted, so kidney biopsy was performed. The pathological findings showed diffuse thin basement membrane and partial basket-weave change. Then he was conducted a gene test at the age of 4. He exhibited moderate proteinuria (0.68 g/g creatinine) and hematuria, and his serum albumin was slightly low (3.5 g/dl). He had bilateral hyperopia but no deafness or kidney dysfunction. There was no familial history of ESRD. He diagnosed with XLAS by gene testing, which showed a large hemizygous deletion from exon 3 to 51 in COL4A5 detected by next-generation sequencing and then confirmed by multiplex ligation-dependent probe amplification (MLPA). Then, MLPA analysis revealed that the female patient had the same deletion with only a 20% copy number reduction compared with a normal female control; she was thus diagnosed with XLAS with somatic mosaicism.
Discussion
Previous XLAS cases with somatic mosaicism in COL4A5 had SNVs, and these changes could be detected by sequencing analysis. In contrast, our case had somatic mosaicism of CNVs in COL4A5. CNVs in COL4A5 are relatively rare (5%) and, CNVs were usually detected by the absence of PCR products or MLPA. This case clearly featured a germline variant because the patient’s son exhibited XLAS. In conclusion, this is the first case report with somatic and germline mosaicism caused by CNVs in an XLAS patient detected by MLPA. This information was important for the genetic counseling of this affected family.