Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta
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ORIGINAL ARTICLE
Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta Lei Xi1 · Hao Zhang1 · Zhen‑Lin Zhang1 Received: 1 June 2020 / Accepted: 1 October 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020
Abstract Introduction Osteogenesis imperfecta (OI) is a well-known heritable disorder of connective tissue characterized by skeletal fragility and low bone mass. Nearly 90% of patients with OI have disease variants in COL1A1 and COL1A2 that encode for the α1 and α2 chains of type I collagen. Materials and methods A retrospective analysis of 185 probands who were diagnosed with OI in Shanghai Jiao Tong University Affiliated Sixth People’s Hospital from March 2005 to December 2019 was performed. Results A total of 140 mutations in COL1A1 and 45 mutations in COL1A2 were identified, of which 18 variations were novel. In the phenotype analysis, there were more sporadic cases than familial OI cases in China (54.6% vs. 45.4%, P T c.3815G > T
p.Glu25AlafsX48 p.Pro150ArgfsX13 p.Gly215Asp Putative aberrant splicing Putative aberrant splicing p.Gly326Val p.Gly362Ala p.Gly383Ala p.Ala1075ProfsX33 p.Gly1145TrpfsX29 p.Asn1156LysfsX18 p.Gly1181AlafsX58 p.Trp1312X p.Gly694Asp p.Ala702Gly p.Val987_Pro989dup p.Asp1120Val p.Cys1272Phe
I I III I I I I III III I I I IV I I IV I I
patients with type III, 33 (17.8%) patients with type IV OI. There was no remarkable difference in gender between different genes (P = 0.491) and there was no difference in age of onset and visit between patients with qualitative mutations and those with quantitative mutations (P = 0.217, Table 3). Compared with patients with haploinsufficiency, patients with helical glycine mutations had lower BMD at the lumbar spine (Z-score, − 2.3 ± 0.8, P = 0.016) and femoral neck (Z-score, − 1.8 ± 1.0,
Journal of Bone and Mineral Metabolism Table 3 Relationship between clinical features and mutation types (helical mutation vs. haploinsufficiency) in COL1A1 and COL1A2 Collagen type I mutation
P value
Helical mutation Haploinsufficiency Male/female OI type (I/III/IV) Age of visit (year) Age of onset (year) Ca (mmol/L) P (mmol/L) ALP (U/L) β-CTX (ng/L) 25OHD (ng/ml) PTH (pg/mL) Height Z score Weight Z score LS-BMD Z score FN-BMD Z score Number of fractures Positive family history Scoliosis Blue sclerae DI Hearing loss
34/27 36/18/7 13.6 ± 10.1 2.9 ± 6.2 2.4 ± 0.3 1.4 ± 0.3 216.0 ± 94.0 472.2 ± 144.4 23.5 ± 4.4 28.3 ± 7.0 − 1.1 ± 2.0 − 0.8 ± 2.2 − 2.3 ± 0.8 − 1.8 ± 1.0 5.2 ± 2.3
36/10 31/9/6 10.6 ± 5.0 4.6 ± 6.7 2.4 ± 0.1 1.5 ± 0.4 197.6 ± 90.2 545.6 ± 142.6 24.6 ± 5.0 28.0 ± 6.8 − 1.3 ± 1.6 − 1.0 ± 2.3 − 1.6 ± 1.4 − 1.1 ± 1.1 3.6 ± 1.5
0.015 0.624 0.073 0.217 0.463 0.440 0.418 0.059 0.409 0.889 0.604 0.741 0.016 0.042 < 0.001
17(28%)
27(59%)
0.001
3(5%) 39(64%) 21(34%) 0
5(11%) 29(63%) 13(28%) 3(7%)
0.251 0.659 0.187 0.044
BMD bone mineral density, DI dentinogenesis imperfect, ALP alkaline phosphatase, β-CTX β-isomerized carboxy-telopeptide of type I collagen, 25OHD 25
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