Abstract
X-linked Alport syndrome (XLAS) is a progressive hereditary kidney disease caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain. To date, 11 cases having somatic mosaic variants in COL4A5 have been reported; however, all of them involved single-nucleotide variations (SNVs). Here, we report a female XLAS patient with somatic mosaicism identified by copy number variation (CNV) in COL4A5. The case was a 35-year-old female, the mother of the proband, whose only clinical symptom was hematuria. The proband, who was the son of this patient, was diagnosed with XLAS by gene testing, which showed a large hemizygous deletion from exon 3–51 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. CNVs in COL4A5 are relatively rare and, to the best of our knowledge, somatic mosaic variants with CNVs have never been reported. This case clearly featured a germline variant because the patient’s son exhibited XLAS. This is thus the first case report on an XLAS patient having CNV in COL4A5 with somatic mosaicism. The obtained findings were very important for the genetic counseling of this family.
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Acknowledgments
We thank Edanz (www.edanzediting.co.jp) for editing the English text of a draft of this manuscript.
Funding
This study was supported by Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (subject ID: 17H04189 to Kazumoto Iijima and 19K08726 to Kandai Nozu), and by the Japan Agency for Medical Research and Development (AMED) (Grant Number JP19ek0109231h0003 to Kandai Nozu and Kazumoto Iijima).
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Kazumoto Iijima has received grant support from Daiichi Sankyo Co., Ltd., as well as consulting fees from Takeda Pharmaceutical Company and Kyowa Hakko Kirin Co., Ltd. Kandai Nozu has received lecture fees from Novartis Pharmaceuticals Corporation. Kazumoto Iijima and Kandai Nozu have filed a patent application regarding the development of antisense nucleotides for exon-skipping therapy in Alport syndrome.
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee at Kobe University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Aoto, Y., Kise, T., Nakanishi, K. et al. A case with somatic and germline mosaicism in COL4A5 detected by multiplex ligation-dependent probe amplification in X-linked Alport syndrome. CEN Case Rep 9, 431–436 (2020). https://doi.org/10.1007/s13730-020-00503-8
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DOI: https://doi.org/10.1007/s13730-020-00503-8