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Atypical phenotypes and novel OCRL variations in southern Chinese patients with Lowe syndrome

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Abstract

Background

Lowe syndrome is characterized by the presence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study presents a case of an atypical phenotype, investigates the genetic characteristics of eight children diagnosed with Lowe syndrome in southern China, and performs functional analysis of the novel variants.

Methods

Whole-exome sequencing was conducted on eight individuals diagnosed with Lowe syndrome from three medical institutions in southern China. Retrospective collection and analysis of clinical and genetic data were performed, and functional analysis was conducted on the five novel variants.

Results

In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not present with congenital cataracts. Common features among all patients included cognitive impairment, short stature, and low molecular weight proteinuria. Eight variations in the OCRL gene were identified, encompassing three previously reported and five novel variations. Among the novel variations, three nonsense mutations were determined to be pathogenic, and two patients harboring novel missense variations of uncertain significance exhibited severe typical phenotypes. Furthermore, all novel variants were associated with altered protein expression levels and impacted primary cilia formation.

Conclusion

This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and performs a functional analysis of novel variants in the OCRL gene, thereby expanding the understanding of the clinical manifestations and genetic diversity associated with Lowe syndrome.

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Data availability

The corresponding author can provide the data supporting the findings of this study upon reasonable request.

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Acknowledgements

The authors express their gratitude to the participating families for their involvement in this study. Appreciation is also extended to the medical detection departments of hospitals for their valuable support in conducting imaging and biochemical examinations.

Funding

This work was supported by the Enterprise Joint Fund of Guangdong Basic and Applied Basic Research Fund (Public Health and Medical Health) (grant number 2021A1515220168).

Author information

Authors and Affiliations

  1. Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, Guangzhou Medical University, Guangzhou, 510623, China

    Rong Du, Chengcheng Zhou, Shehong Chen, Yunting Lin, Aijing Xu, Huifen Mei, Ruidan Zheng, Cuili Liang, Yanna Cai, Yongxian Shao, Wen Zhang, Li Liu & Chunhua Zeng

  2. Department of Pediatric Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China

    Tong Li

  3. Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children’s Medical Center Liuzhou Hospital, Liuzhou, 545000, China

    Rong Du, Huifen Mei, Dongdong Tan, Wen Zhang, Li Liu & Chunhua Zeng

  4. Department of Pediatric Neurology, Guangzhou Women and Children’s Medical Center Liuzhou Hospital, Liuzhou, 545000, China

    Xiaoli Huang

  5. Department of Guangzhou Newborn Screening Center, Guangzhou Women and Children’s Medical Center, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, Guangzhou Medical University, Guangzhou, 510623, China

    Yonglan Huang

  6. Department of Pediatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China

    Shehong Chen

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  1. Rong Du
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  2. Chengcheng Zhou
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  16. Li Liu
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  17. Chunhua Zeng
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Contributions

CZ, LL, and WZ designed the study. RD, TL, AX, YH, HM, DT, XH, RZ, CL, WZ, LL, and CZ obtained clinical information. RD, CZH, SC, YL, YS, and YC conducted the experiments. RD and CZ performed data analysis. RD authored the paper. RD and CZ reviewed and revised the paper. All authors approved of the manuscript prior to submission.

Corresponding author

Correspondence to Chunhua Zeng.

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Ethics approval

The research involving human participants underwent ethical review and received approval from the Institutional Review Board of Guangzhou Women and Children’s Medical Center. Written informed consent was obtained from the legal guardian of each participant prior to their involvement in the study.

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Rong Du, Chengcheng Zhou, and Shehong Chen contributed to the work equally and should be regarded as co-first authors.

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Du, R., Zhou, C., Chen, S. et al. Atypical phenotypes and novel OCRL variations in southern Chinese patients with Lowe syndrome. Pediatr Nephrol (2024). https://doi.org/10.1007/s00467-024-06356-y

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