COQ6 Mutations in Children With Steroid-Resistant Focal Segmental Glomerulosclerosis and Sensorineural Hearing Loss

doi:10.1053/j.ajkd.2016.10.040

American Journal of Kidney Diseases

Volume 70, Issue 1, July 2017, Pages 139-144

https://doi.org/10.1053/j.ajkd.2016.10.040 Get rights and content

The phenotypic combination of steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) and sensorineural hearing loss has been mainly reported in patients with mitochondrial cytopathies, including primary coenzyme Q10 (CoQ10) deficiency. In this report of 10 children with SR-FSGS and sensorineural hearing loss, we found 6 patients with biallelic COQ6 mutations. Median age at the onset of nephrotic syndrome was 29 (range, 15-47) months. All patients progressed to end-stage renal disease within a median of 13 (range, 1-27) months after the onset. Kidney biopsy revealed abnormal mitochondrial proliferation in podocytes in all 6 patients. None of the 5 patients who underwent kidney transplantation developed recurrence of FSGS. Primary CoQ10 deficiency due to COQ6 mutations should be considered in children presenting with both SR-FSGS and sensorineural hearing loss. An early diagnosis of COQ6 mutations is essential because the condition is treatable when CoQ10 supplementation is started at the early stage. We recommend early kidney biopsy because detection of abnormal mitochondrial proliferation in podocytes might provide an earlier diagnostic clue.

Section snippets

Case Reports

In mutational analyses focused mainly on primary CoQ10 deficiency in 10 unrelated Korean children with SR-FSGS and sensorineural hearing loss, we detected 6 patients with biallelic COQ6 mutations and 1 patient with a single heterozygous c.782C>T mutation in COQ6 (Table 1). In the other 3 patients, no pathogenic mutation was detected in any of the genes tested in this study (detailed methods are given in Item S1, available as online supplementary material). Cosegregation of the biallelic COQ6

Discussion

In this report of 10 children with SR-FSGS and sensorineural hearing loss, we identified 6 patients harboring compound heterozygous COQ6 mutations together with abnormal mitochondrial proliferation in podocytes. There was one additional patient with a single heterozygous COQ6 mutation. Although the patient had a phenotype almost identical to the patients with compound heterozygous mutations, we excluded this patient from the genotype-phenotype analyses due to an incomplete genetic diagnosis.

Acknowledgements

Support: This study was supported by grant HI12C0014 of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea.

Financial Disclosure: The authors declare that they have no relevant financial interests.

Peer Review: Evaluated by 3 external peer reviewers, a pathologist, a Co-Editor, and Editor-in-Chief Levey.

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The majority of the COQ2 patients presented before the age of 2 years (14/30, 47%) [121,136,150,201,202]. This is also true for PDSS1 (2/3, 67%) [152], PDSS2 (4/7, 57%) [121,169] and COQ6 (15/30, 50%) [119,179,193,198,203,211] patients. Some probands with pathogenic variants of COQ4 (11/35, 31%) [83,147,149], COQ7 (1/3, 33%) [141], COQ9 (1/7, 14%) [158], COQ8A (23/77, 30%) [115,117,163,180,184–186] and COQ8B (4/79, 5%) [120,188] also presented when they were 2 years old or before.
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Case ReportCOQ6 Mutations in Children With Steroid-Resistant Focal Segmental Glomerulosclerosis and Sensorineural Hearing Loss

Section snippets

Case Reports

Discussion

Acknowledgements

Cell

Lancet

Kidney Int

Kidney Int

A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome

J Am Soc Nephrol

Rapid detection of monogenic causes of childhood-onset steroid-resistant nephrotic syndrome

Clin J Am Soc Nephrol

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort

Clin J Am Soc Nephrol

Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression

J Am Soc Nephrol

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia

Nat Genet

Human lamininβ2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities

Hum Mol Genet

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Nat Genet

Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Hegglin/Fechtner Syndrome Consortium

Nat Genet

The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation

J Am Soc Nephrol

Genetics of coenzyme Q10 deficiency

Mol Syndromol

Case Report
COQ6 Mutations in Children With Steroid-Resistant Focal Segmental Glomerulosclerosis and Sensorineural Hearing Loss