TY - JOUR
T1 - Genotypic and Phenotypic Analysis in Chinese Cohort With Autosomal Recessive Osteogenesis Imperfecta
AU - Li, Shan
AU - Cao, Yixuan
AU - Wang, Han
AU - Li, Lulu
AU - Ren, Xiuzhi
AU - Mi, Huan
AU - Wang, Yanzhou
AU - Guan, Yun
AU - Zhao, Feiyue
AU - Mao, Bin
AU - Yang, Tao
AU - You, Yi
AU - Guan, Xin
AU - Yang, Yujiao
AU - Zhang, Xue
AU - Zhao, Xiuli
N1 - Funding Information:
We thank all the OI patients and their families for their participation. Funding. This study was supported by grants from National Key Research and Development Program of China (2016YFE0128400 and 2016YFC0905100), CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-3-003), and National Natural Science Foundation of China (81472053).
Publisher Copyright:
© Copyright © 2020 Li, Cao, Wang, Li, Ren, Mi, Wang, Guan, Zhao, Mao, Yang, You, Guan, Yang, Zhang and Zhao.
PY - 2020/9/15
Y1 - 2020/9/15
N2 - Osteogenesis imperfecta (OI) is a rare heritable skeletal disorder which is mainly caused by defected type I collagen. Autosomal recessive OI (AR-OI) is caused by mutations of genes that are responsible for type I collagen modification and folding, and is often associated with more severe phenotypes. Due to the limited number of recessive OI patients, it has been difficult to study the mutation spectrum as well as the correlation of genotype and phenotype. This study recruited a Chinese cohort of 74 AR-OI families, aiming to establish the mutation spectrum and to examine the genotypic and phenotypic correlation. We identified 82 variants including 25 novel variants and 57 HGMD reported variants in these AR-OI patients, using whole exome sequencing/panel sequencing combined with Sanger sequencing. Pathogenic mutations were found at WNT1 (n = 30, 40.54%), SERPINF1 (n = 22, 29.73%), FKBP10 (n = 10, 13.51%), CRTAP (n = 3, 4.05%), P3H1 (n = 3, 4.05%), SERPINH1 (n = 2, 2.70%), SEC24D (n = 3, 4.05%), and PLOD2 (n = 1, 1.35%) respectively. Thus, WNT1 represents the most frequent pathogenic gene of AR-OI in Chinese population. The most common clinical manifestations of AR-OI patients include walking problem (72.86%), scoliosis (65.28%) and frequent fractures (fractures ≥2/year) (54.05%). Interestingly, ptosis represents a unique phenotype of patients carrying WNT1 variants, and it was rare in patients harboring other pathogenic genes. Our study expanded the mutation spectrum of AR-OI and enriched the knowledge of genotypic and phenotypic correlation in Chinese cohort with AR-OI.
AB - Osteogenesis imperfecta (OI) is a rare heritable skeletal disorder which is mainly caused by defected type I collagen. Autosomal recessive OI (AR-OI) is caused by mutations of genes that are responsible for type I collagen modification and folding, and is often associated with more severe phenotypes. Due to the limited number of recessive OI patients, it has been difficult to study the mutation spectrum as well as the correlation of genotype and phenotype. This study recruited a Chinese cohort of 74 AR-OI families, aiming to establish the mutation spectrum and to examine the genotypic and phenotypic correlation. We identified 82 variants including 25 novel variants and 57 HGMD reported variants in these AR-OI patients, using whole exome sequencing/panel sequencing combined with Sanger sequencing. Pathogenic mutations were found at WNT1 (n = 30, 40.54%), SERPINF1 (n = 22, 29.73%), FKBP10 (n = 10, 13.51%), CRTAP (n = 3, 4.05%), P3H1 (n = 3, 4.05%), SERPINH1 (n = 2, 2.70%), SEC24D (n = 3, 4.05%), and PLOD2 (n = 1, 1.35%) respectively. Thus, WNT1 represents the most frequent pathogenic gene of AR-OI in Chinese population. The most common clinical manifestations of AR-OI patients include walking problem (72.86%), scoliosis (65.28%) and frequent fractures (fractures ≥2/year) (54.05%). Interestingly, ptosis represents a unique phenotype of patients carrying WNT1 variants, and it was rare in patients harboring other pathogenic genes. Our study expanded the mutation spectrum of AR-OI and enriched the knowledge of genotypic and phenotypic correlation in Chinese cohort with AR-OI.
KW - Chinese cohort
KW - WNT1
KW - autosomal recessive osteogenesis imperfecta
KW - mutation spectrum
KW - phenotype
UR - http://www.scopus.com/inward/record.url?scp=85091837081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091837081&partnerID=8YFLogxK
U2 - 10.3389/fgene.2020.00984
DO - 10.3389/fgene.2020.00984
M3 - Article
C2 - 33093841
AN - SCOPUS:85091837081
SN - 1664-8021
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 984
ER -