Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

Nephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. Exploring the correlation between the phenotype and genotype of NPHP-RC is helpful for early diagnosis and management. We investigated the phenotype and genotype spectra of NPHP-RC in a Chinese multicentre cohort. Crosss-ectional and longitudinal data of 60 patients from 57 families with pathogenic NPHP-RC gene mutations distributed in 22 regions of China were collected into a unified, anonymous database. The mean observation time of this cohort was 3.5±3.1 years. Mutations in NPHP1 and NPHP3 were the most common genetic defects. Overall, 45% of patients presented with isolated nephronophthisis (NPH), and 55% exhibited the extrarenal phenotype, which frequently involved the liver (41.7%, n=25), central nervous system (26.7%, n=16), eyes (26.7%, n=16) and skeletal system (11.7%, n=7). Accidental detection of elevated serum creatinine and non-specific symptoms caused by chronic kidney disease occurred in 65% of patients. Patients carrying NPHP1 mutations mainly presented with isolated NPH (90%, 18/20) and progressed to ESRD at a mean age of 12.9±0.5 years. The mean age of ESRD onset in the non-NPHP1 group was lower than that in the NPHP1 group (6.2±1.4 years, p<0.001), especially for patients carrying NPHP3 mutations (3.1±1.2 years), showing a heterogeneous phenotype characterised by Bardet-Biedl syndrome (12.5%, n=5), Joubert syndrome (7.5%, n=3), COACH syndrome (2.5%, n=1), Mainzer-Saldino syndrome (2.5%, n=1), short-rib thoracic dysplasia (2.5%, n=1) and unclassified symptoms (32.5%, n=13). The Chinese Children Genetic Kidney Disease Database registry characterised the spectrum of the phenotype and genotype of NPHP-RC in the Chinese population. NPHP1 and NPHP3 were the most common pathogenic genes. Rapid progression to ESRD and liver involvement were noted in patients with NPHP3 mutations. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Citation

Xiaoshan Tang, Cuihua Liu, Xiaorong Liu, Jing Chen, Xiaoyan Fan, Jialu Liu, Duan Ma, Guanghai Cao, Zhi Chen, Daliang Xu, Ying Zhu, Xiaoyun Jiang, Lizhi Cheng, Yubing Wu, Ling Hou, Yuhong Li, Xiaoshan Shao, Shasha Zheng, Aihua Zhang, Bixia Zheng, Shan Jian, Zanhua Rong, Qingxiao Su, Xia Gao, Jia Rao, Qian Shen, Hong Xu, Chinese Children Genetic Kidney Disease Database (CCGKDD), “Internet Plus” Nephrology Alliance of the National Center for Children’s Care. Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy. Journal of medical genetics. 2022 Feb;59(2):147-154

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PMID: 33323469

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