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. 2025 Jan 14:12:1378083.
doi: 10.3389/fped.2024.1378083. eCollection 2024.

Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review

Lei Zhang #  1 , Gentzon Hall #  2 , Peitong Han  1 , Chunzhen Li  1 , Jieyuan Cui  1
Affiliations

Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review

Lei Zhang et al. Front Pediatr. .

Abstract

Background: Primary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS).

Methods: Four SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing.

Results: Clinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease.

Conclusions: COQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.

Keywords: COQ8B variant; autosomal recessive; focal segmental glomerulosclerosis; glomerulopathy; steroid-resistant nephrotic syndrome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Family 1 Pedigree - Cases 2 and 3 both carried homozygous variants of COQ8B with in exon 9 (c.737G>A) while both parents heterozygously carried the same variant. (B) Family 2 Pedigree - Case 4 carried two heterozygous variants, c.737G>A (a) and c.1465C>T (d) in COQ8B. While his mother and father heterozygously carried c.737G>A (c) and c.1465C>T (e), respectively.
Figure 2
Figure 2
Genomic Structure of COQ8B and Family Sequencing -COQ8B gene structure with labeling of family variants in exons 9 and 15. Direct sequencing data for Family 1 showing 2 affected siblings with the homozygous COQ8B variant (c.737G>A) and both unaffected parents with a heterozygous COQ8B variants. Direct sequencing data for Family 2 showing 1 affected individual with a compound heterozygous variants (c.737G>A and c.1465C>T) of COQ8B and each unaffected parent with a single heterozygous variant.
Figure 3
Figure 3
Predicted effect of family COQ8B variants on protein secondary structure – COQ8B domain structure depicted with p.S246N and p.H489Y variants labeled (*). Both variants are predicted to disrupt the secondary structure of the protein.
Figure 4
Figure 4
(a) Family proteinuria response trajectories - change in proteinuria during coenzyme Q10 (CoQ10) supplementation over 2 years of follow-up (F1-Ⅲ-2, F1-Ⅲ-3 and F2-Ⅲ-1 correspond to case 2,3 and 4). (b) Family eGFR Response Trajectories – Change in serum creatinine during coenzyme Q10 (CoQ10) supplementation over 2 years of follow-up (F1-Ⅲ-2, F1-Ⅲ-3 and F2-Ⅲ-1 correspond to case 2,3 and 4).
Figure 5
Figure 5
Renal histopathology - (a) renal histopathology of case 4 showing FSGS by H&E staining and (b) Silver Jones Methenamine staining.
See this image and copyright information in PMC

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References

    1. AbuMaziad AS, Thaker TM, Tomasiak TM, Chong CC, Galindo MK, Hoyme HE. The role of novel COQ8B mutations in glomerulopathy and related kidney defects. Am J Med Genet A. (2021) 185:60–7. 10.1002/ajmg.a.61909 - DOI - PubMed
    1. Vazquez Fonseca L, Doimo M, Calderan C, Desbats MA, Acosta MJ, Cerqua C, et al. Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function. Hum Mutat. (2018) 39:406–14. 10.1002/humu.23376 - DOI - PMC - PubMed
    1. Zhu X, Zhang Y, Yu Z, Yu L, Huang W, Sun S, et al. The clinical and genetic features in Chinese children with steroid-resistant or early-onset nephrotic syndrome: a multicenter cohort study. Front Med. (2022) 9:885178. 10.3389/fmed.2022.885178 - DOI - PMC - PubMed
    1. Korkmaz E, Lipska-Ziętkiewicz BS, Boyer O, Gribouval O, Fourrage C, Tabatabaei M, et al. ADCK4 - associated glomerulopathy causes adolescence-onset FSGS. J Am Soc Nephrol JASN. (2016) 27:63–8. 10.1681/ASN.2014121240 - DOI - PMC - PubMed
    1. Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V, Lovric S, et al. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J Clin Invest. (2013) 123:5179–89. 10.1172/JCI69000 - DOI - PMC - PubMed

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