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Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.

Accepted version
Peer-reviewed

Type

Article

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Authors

Li, Fucheng 
Yue, Zhihui 
Xu, Tingting 
Chen, Minghui 
Zhong, Liangying 

Abstract

OBJECTIVE: To characterize the phenotypes of Dent disease in Chinese children and their heterozygous mothers and to establish genetic diagnoses. STUDY DESIGN: Using a modified protocol, we screened 1288 individuals with proteinuria. A diagnosis of Dent disease was established in 19 boys from 16 families by the presence of loss of function/deleterious mutations in CLCN5 or OCRL1. We also analyzed 16 available patients' mothers and examined their pregnancy records. RESULTS: We detected 14 loss of function/deleterious mutations of CLCN5 in 15 boys and 2 mutations of OCRL1 in 4 boys. Of the patients, 16 of 19 had been wrongly diagnosed with other diseases and 11 of 19 had incorrect or unnecessary treatment. None of the patients, but 6 of 14 mothers, had nephrocalcinosis or nephrolithiasis at diagnosis. Of the patients, 8 of 14 with Dent disease 1 were large for gestational age (>90th percentile); 8 of 15 (53.3%) had rickets. We also present predicted structural changes for 4 mutant proteins. CONCLUSIONS: Pediatric Dent disease often is misdiagnosed; genetic testing achieves a correct diagnosis. Nephrocalcinosis or nephrolithiasis may not be sensitive diagnostic criteria. We identified 10 novel mutations in CLCN5 and OCRL1. The possibility that altered CLCN5 function could affect fetal growth and a possible link between a high rate of rickets and low calcium intake are discussed.

Description

Keywords

diagnosis, mutations, nephrocalcinosis, nephrolithiasis, structural modeling, Adolescent, Adult, Asian People, Child, Child, Preschool, China, Chloride Channels, Dent Disease, Female, Fetal Development, Heterozygote, Humans, Male, Mothers, Mutation, Phenotype, Phosphoric Monoester Hydrolases

Journal Title

J Pediatr

Conference Name

Journal ISSN

0022-3476
1097-6833

Volume Title

174

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (096956/Z/11/Z)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0514-10122)