title: Identification of a novel mutation in the CLCN5 gene in a Chinese family with Dent-1 disease.
abstract: Dent disease comprises a group of X-linked recessive inherited renal tubular disorders, the symptoms of which include low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and progressive renal failure. We sought to characterize the clinical manifestations and to identify the mutations associated with this disease in Chinese patients. In total, 155 DNA samples were collected from one affected individual, four of his family members, and 150 healthy donors. All 12 exons and the exon-intron boundaries of the CLCN5 gene were amplified and directly sequenced in this Chinese family. The proband demonstrated osteomalacia, which had resulted in more than 10 fractures, LMWP, and renal failure. A single base 'G' deletion at nucleotide 246 (c. 246delG) was identified in exon 5 of the CLCN5 gene in this patient, resulting in a frame shift mutation (fsX) that changed the Threonine (Thr) residue in position 83 to Proline (Pro). The proband's mother was found to be a carrier of this mutation. The present study suggests that a novel frameshift mutation (c. 246delG) in exon 5 of the CLCN5 gene is responsible for Dent disease in this case. Our findings also expand the known spectrum of CLCN5 mutations.
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Yue
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.forename: Jie-Mei
authors.initials: JM
authors.lastname: Gu
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Liu
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000328:Adult; D018118:Chloride Channels / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D053040:Nephrolithiasis / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels
keywords: CLCN5 gene; dent disease; low-molecular-weight proteinuria; mutation; rickets