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Calcif Tissue Int. 2018 Mar;102(3):296-309. doi: 10.1007/s00223-017-0360-6. Epub 2017 Nov 24.

Novel Mutations in PLOD2 Cause Rare Bruck Syndrome.

Lv F1, Xu X1, Song Y1, Li L1, Asan2,3,4, Wang J2,3,4, Yang H2,3,4, Wang O1, Jiang Y1, Xia W1, Xing X1, Li M5.

Author information

1
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Shuaifuyuan No.1, Dongcheng District, Beijing, 100730, China.
2
Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China.
3
Tianjin Enterprise Key Laboratory of Clinical Molecular Diagnostic, BGI-Shenzhen, Tianjin, 300308, China.
4
BGI-Shenzhen, Shenzhen, 518083, China.
5
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Shuaifuyuan No.1, Dongcheng District, Beijing, 100730, China. limeilzh@sina.com.

Abstract

Bruck syndrome is a rare autosomal recessive form of osteogenesis imperfecta (OI), which is mainly characterized by joint contractures and recurrent fragility fractures. Mutations in FKBP10 and PLOD2 were identified as the underlying genetic defects of Bruck syndrome. Here we investigated the phenotypes and the pathogenic mutations of three unrelated Chinese patients with Bruck syndrome. Clinical fractures, bone mineral density (BMD), bone turnover biomarkers, and skeletal images were evaluated in detail. The pathogenic mutations were identified by targeted next-generation sequencing and subsequently confirmed by Sanger sequencing and cosegregation analysis. We also evaluated the effects of zoledronic acid on bone fracture incidence and BMD of the patients. Three patients had congenital joint contractures, recurrent fragility fractures, camptodactyly, clubfoot, scoliosis, but without dentinogenesis imperfecta and hearing loss. Five novel heterozygous mutations were detected in PLOD2, including three heterozygous missense mutations (c.1138C>T, p.Arg380Cys; c.1153T>C, p.Cys385Arg; and c.1982G>A, p.Gly661Asp), one heterozygous nonsense mutation (c.2038C>T, p.Arg680X), and one heterozygous splice-site mutation (c.503-2A>G). Their parents were all heterozygous carriers of these mutations in PLOD2. No clear genotype-phenotype correlations were found in these patients with PLOD2 mutations. Z-score of BMD was significantly increased, but scoliosis progressed and new bone fractures occurred during the treatment of zoledronic acid. Our findings expanded the spectrum of gene mutations of Bruck syndrome.

KEYWORDS:

Bruck syndrome; Osteogenesis imperfecta; PLOD2 mutations

PMID:
29177700
DOI:
10.1007/s00223-017-0360-6
[Indexed for MEDLINE]

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