PT  - JOURNAL ARTICLE
AU  - Xiaoshan Tang
AU  - Cuihua Liu
AU  - Xiaorong Liu
AU  - Jing Chen
AU  - Xiaoyan Fan
AU  - Jialu Liu
AU  - Duan Ma
AU  - Guanghai Cao
AU  - Zhi Chen
AU  - Daliang Xu
AU  - Ying Zhu
AU  - Xiaoyun Jiang
AU  - Lizhi Cheng
AU  - Yubing Wu
AU  - Ling Hou
AU  - Yuhong Li
AU  - Xiaoshan Shao
AU  - Shasha Zheng
AU  - Aihua Zhang
AU  - Bixia Zheng
AU  - Shan Jian
AU  - Zanhua Rong
AU  - Qingxiao Su
AU  - Xia Gao
AU  - Jia Rao
AU  - Qian Shen
AU  - Hong Xu
AU  - Chinese Children Genetic Kidney Disease Database (CCGKDD)
ED  - ,
TI  - Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy
AID  - 10.1136/jmedgenet-2020-107184
DP  - 2022 Feb 01
TA  - Journal of Medical Genetics
PG  - 147--154
VI  - 59
IP  - 2
4099  - http://jmg.bmj.com/content/59/2/147.short
4100  - http://jmg.bmj.com/content/59/2/147.full
SO  - J Med Genet2022 Feb 01; 59
AB  - Background 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.Methods 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.Results 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).Conclusions 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.Data are available on reasonable request. The data that support the findings of this study are available from the corresponding author on reasonable request.