• Yi Liu, Lijie Song, Doudou Ma, Fang Lv, Xiaojie Xu, Jianyi Wang, Weibo Xia, Yan Jiang, Ou Wang, Yuwen Song, Xiaoping Xing, Asan BGI Shenzhen: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China; Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China., and Mei Li.
• Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
• Clin. Chim. Acta. 2016 Oct 1; 461: 172-80.

BackgroundsOsteogenesis imperfecta (OI) is a rare inherited disease characterized by increased bone fragility and vulnerability to fractures. Recently, WNT1 is identified as a new candidate gene for OI, here we detect pathogenic mutations in WNT1 and analyze the genotype-phenotype association in four Chinese families with OI.MethodsWe designed a targeted next generation sequencing panel with known fourteen OI-related genes. We applied the approach to detect pathogenic mutations in OI patients and confirmed the mutations with Sanger sequencing and cosegregation analysis. Clinical fractures, bone mineral density (BMD) and the other clinical manifestations were evaluated. We also observed the effects of bisphosphonates in OI patients with WNT1 mutations.ResultsFour compound heterozygous mutations (c.110T>C; c.505 G>T; c. 385G>A; c.506 G>A) in WNT1 were detected in three unrelated families. These four mutations had not been reported yet. A recurrent homozygous mutation (c.506dupG) was identified in the other two families. These patients had moderate to severe OI, white to blue sclera, absence of dentinogenesis imperfecta and no brain malformation. We did not observe clear genotype-phenotype correlation in WNT1 mutated OI patients. Though bisphosphonates increased BMD in WNT1 related OI patients, height did not increase and fracture continued.ConclusionsWe reported four novel heterozygous variants and confirmed a previous reported WNT1 mutation in four Chinese families with a clinical diagnosis of OI. Our study expanded OI spectrum and confirmed moderate to severe bone fragility induced by WNT1 defects.Copyright © 2016 Elsevier B.V. All rights reserved.

16 keywords...

hide…