Genotypic and Phenotypic Analysis in Chinese Cohort With Autosomal Recessive Osteogenesis Imperfecta.
Genotypic and Phenotypic Analysis in Chinese Cohort With Autosomal Recessive Osteogenesis Imperfecta.
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DOI：
10.3389/fgene.2020.00984
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发表时间：
2020
影响因子：
3.7
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Li S;Cao Y;Wang H;Li L;Ren X;Mi H;Wang Y;Guan Y;Zhao F;Mao B;Yang T;You Y;Guan X;Yang Y;Zhang X;Zhao X
骨生成障碍是一种罕见的遗传性骨骼疾病，主要由I型胶原缺陷引起。常染色体隐性遗传性OI（AR-OI）是由负责I型胶原蛋白修饰和折叠的基因突变引起的，通常与更严重的表型相关。由于隐性遗传型OI患者的数量有限，研究其突变谱以及基因型与表型的相关性一直是困难的。本研究招募了74个AR-OI家系，旨在建立突变谱，并检查基因型和表型相关性。我们在这些AR-OI患者中鉴定了82种变异，包括25种新的变异和57种HGMD报告的变异，使用全外显子组测序/面板测序结合桑格测序。在WNT 1位点发现致病性突变（n = 30，40.54%），SERPINF 1（n = 22，29.73%），FKBP 10（n = 10，13.51%）、CRTAP（n = 3，4.05%）、P3H1（n = 3，4.05%）、SERPINH1（n = 2，2.70%）、SEC24D（n = 3，4.05%）和PLOD 2（n = 1，1.35%）。因此，WNT 1是中国人群中最常见的AR-OI致病基因。最常见的临床表现为行走困难（72.86%）、脊柱侧凸（65.28%）和频繁骨折（骨折≥2次/年）（54.05%）。有趣的是，上睑下垂代表了携带WNT 1变体的患者的独特表型，并且在携带其他致病基因的患者中很少见。我们的研究扩大了AR-OI的突变谱，丰富了中国AR-OI人群基因型和表型相关性的知识。
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.
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作者：
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