Journal of Nephrology

, Volume 32, Issue 1, pp 155–159 | Cite as

Germline mosaicism is a pitfall in the diagnosis of “sporadic” X-linked Alport syndrome

  • Takayuki OkamotoEmail author
  • Kandai Nozu
  • Kazumoto Iijima
  • Tadashi Ariga
Case Report


Approximately 80% of patients with Alport syndrome have X-linked Alport syndrome (XLAS), which is caused by mutations in the type IV collagen alpha 5 gene (COL4A5). In patients with XLAS, approximately 10–15% of COL4A5 mutations occur as spontaneous events. Here, we describe maternal germline mosaicism in a family of XLAS patients. Since our patient’s parents showed normal urinary findings without COL4A5 mutation using genomic DNA isolated from peripheral leukocytes, the patient was initially diagnosed with “sporadic” XLAS. However, genetic analysis of the patient’s sister with microscopic hematuria identified the same COL4A5 heterozygous mutation. Therefore, we concluded that our patient and the sister had XLAS caused by maternal germline mosaicism, not “sporadic” XLAS. Our case suggests that “sporadic” XLAS may in some patients be caused by the transmission of an abnormal allele from either parent with germline mosaicism in COL4A5. Germline mosaicism is thought to be rare, but we should consider that even asymptomatic parents of “sporadic” XLAS patients could carry a somatic and/or germline mosaicism. More cautious genetic counseling is advisable for all “sporadic” XLAS patients. Furthermore, urinalysis screening of “sporadic” XLAS patients’ siblings is also important to enable an earlier detection of parental germline mosaicism.


Genetic counseling Germline mosaicism Isolated XLAS 



We thank Masanori Nakanishi and Ryota Suzuki (Department of Pediatrics, Kushiro Red Cross Hospital, Kushiro, Japan) for providing us medical information on the patient and his family. We also thank Tomohiko Yamamura and Tomoko Horinouchi (Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan) for genetic examinations.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

40620_2018_518_MOESM1_ESM.tif (9.2 mb)
Sequencing results of the patient’s mother to evaluate the existence of somatic mosaicism. Sanger sequence of saliva and urinary cells was also performed in the patient’s mother, resulting in no COL4A5 mutations in these samples or in her peripheral leukocytes (TIF 9442 KB)
40620_2018_518_MOESM2_ESM.tif (26 mb)
Targeted sequence analysis for genomic DNA extracted from saliva and peripheral leukocytes to pick up low grade mosaicism in somatic cells. No variant was detected in both samples although the NGS depth was 179 and 259 respectively. These results indicated the existence of maternal germline mosaicism without somatic mosaicism in COL4A5. (TIF 26584 KB)


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Copyright information

© Italian Society of Nephrology 2018

Authors and Affiliations

  1. 1.Department of PediatricsHokkaido University Graduate School of MedicineSapporoJapan
  2. 2.Department of PediatricsKobe University Graduate School of MedicineKobeJapan

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