Novel Mutations in SERPINF1 Result in Rare Osteogenesis Imperfecta Type VI
| Autor: | Zi-ying Yang, Jian Wang, A. San, Wei-bo Xia, Li-jie Song, Xiao-ping Xing, Xiao-jie Xu, Fang Lv, Mei Li, Yan Jiang, Yi Liu, Huanming Yang, Jian-yi Wang, Ou Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Heterozygote Adolescent Endocrinology Diabetes and Metabolism Nonsense mutation Biology Compound heterozygosity Frameshift mutation 03 medical and health sciences symbols.namesake Exon Fractures Bone Endocrinology Bone Density medicine Missense mutation Humans Orthopedics and Sports Medicine Genetic Predisposition to Disease Nerve Growth Factors Eye Proteins Serpins Genetics Sanger sequencing Homozygote Intron Osteogenesis Imperfecta medicine.disease 030104 developmental biology Phenotype Osteogenesis imperfecta Mutation symbols Female |
| Zdroj: | Calcified tissue international. 100(1) |
| ISSN: | 1432-0827 |
| Popis: | Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by recurrent fragile fractures. Serpin peptidase inhibitor, clade F, member 1 (SERPINF1) is known to cause a distinct, extremely rare autosomal recessive form of type VI OI. Here we report, for the first time, the detection of SERPINF1 mutations in Chinese OI patients. We designed a novel targeted next-generation sequencing panel of OI-related genes to identify pathogenic mutations, which were confirmed with Sanger sequencing and by co-segregation analysis. We also investigated the phenotypes of OI patients by evaluating bone mineral density, radiological fractures, serum bone turnover markers, and pigment epithelium-derived factor (PEDF) concentration. Six patients with moderate-to-severe bone fragility, significantly low bone mineral density, and severe deformities of the extremities were recruited from five unrelated families for this study. Six pathogenic mutations in SERPINF1 gene were identified, five of which were novel: (1) a homozygous in-frame insertion in exon 3 (c.271_279dup, p.Ala91_Ser93dup); (2) compound heterozygous mutations in intron 3 (c.283 + 1G > T, splicing site) and exon 5 (c.498_499delCA, p.Arg167SerfsX35, frameshift); (3) a homozygous frameshift mutation in exon 8 (c.1202_1203delCA, p.Thr401ArgfsX); (4) compound heterozygous missense mutation (c.184G > A, p.Gly62Ser) and in-frame insertion (c.271_279dup, p.Ala91_Ser93dup) in exon 3; and (5) a heterozygous nonsense mutation in exon 4 (c.397C>T + ?, p.Gln133X + ?). Serum PEDF levels were barely detectable in almost all subjects. We identified five novel mutations in SERPINF1 and confirmed the diagnostic value of serum PEDF level for the first time in Chinese patients with the extremely rare OI type VI. |
| Databáze: | OpenAIRE |
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