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

Autor: Du R; 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.; Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China., Zhou C; 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., Chen S; 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.; Department of Pediatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China., Li T; Department of Pediatric Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Lin Y; 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., Xu A; 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., Huang Y; 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., Mei H; 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.; Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China., Huang X; Department of Pediatric Neurology, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China., Tan D; Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China., Zheng R; 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., Liang C; 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., Cai Y; 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., Shao Y; 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., Zhang W; 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.; Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China., Liu L; 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.; Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China., Zeng C; 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. chunhuazeng@hotmail.com.; Department of Endocrinology, Genetic, and Rare Diseases, Guangzhou Women and Children's Medical Center Liuzhou Hospital, Liuzhou, 545000, China. chunhuazeng@hotmail.com.
Jazyk: angličtina
Zdroj: Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2024 Aug; Vol. 39 (8), pp. 2377-2391. Date of Electronic Publication: 2024 Apr 08.
DOI: 10.1007/s00467-024-06356-y
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)
Databáze: MEDLINE
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