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A novel mutation combining with rs66612022 in a Chinese pedigree suggests a new pathogenesis to osteogenesis imperfecta via whole genome sequencing
Author(s) -
Li Yanjiao,
Liang Hongsuo,
Yuan Dekai,
Liu Baoling,
Liu Ling,
Zhang Yongfa,
Hou Kaiyu,
Zhang Yunchao,
Chen Bin,
Ding Jing,
Li Yunxia,
Wang Qilin,
Wu Haiying,
Shi Hong,
Hu Min
Publication year - 2020
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12371
Subject(s) - osteogenesis imperfecta , missense mutation , genetics , mutation , biology , gene , genetic heterogeneity , phenotype , anatomy
Osteogenesis imperfecta (OI) is a rare heritable disease with systemic connective tissue disorder. Most of the patients represent autosomal dominant form of OI, and are usually resulting from the mutations in type I collagen genes. However, the gene mutations reported previously only account for ∼70% of the OI cases. Here, in a Chinese OI family, we examined seven patients and nine normal individuals using the whole genome sequencing and molecular genetic analysis. The mutation of rs66612022 ( COL1A2 :p.Gly328Ser) related to glycine substitution was found in the seven patients. Moreover, we identified a novel missense mutation ( HMMR :p.Glu2Gln). Interestingly, the individuals of this family with both the mutations were suffering from OI, while the others carried one or none of them are normal. The mutations of COL1A2 and HMMR and their combined effect on OI would further expand the genetic spectrum of OI.