Whole Exome Sequencing with Comprehensive Gene Set Analysis Identified a Biparental-Origin Homozygous c.509G>A Mutation in PPIB Gene Clustered in Two Taiwanese Families Exhibiting Fetal Skeletal Dysplasia during Prenatal Ultrasound

被引:7
作者
Chang, Ting-Yu [1 ,2 ,3 ,4 ,5 ]
Chung, I-Fang [6 ]
Wu, Wan-Ju [1 ,2 ,7 ,8 ]
Chang, Shun-Ping [1 ,2 ]
Lin, Wen-Hsiang [1 ,2 ]
Ginsberg, Norman A. [9 ]
Ma, Gwo-Chin [1 ,2 ,3 ,4 ,10 ,11 ]
Chen, Ming [1 ,2 ,3 ,4 ,7 ,12 ,13 ,14 ,15 ]
机构
[1] Changhua Christian Hosp, Dept Genom Med, Changhua 50046, Taiwan
[2] Changhua Christian Hosp, Ctr Med Genet, Changhua 50046, Taiwan
[3] Changhua Christian Hosp, Res Dept, Changhua 50006, Taiwan
[4] Changhua Christian Hosp Healthcare Syst, Dept Genom Sci & Technol, Changhua 50046, Taiwan
[5] Chung Yuan Christian Univ, Dept Biosci Technol, Taoyuan 32023, Taiwan
[6] Natl Yang Ming Univ, Inst Biomed Informat, Taipei 11221, Taiwan
[7] Changhua Christian Hosp, Dept Obstet & Gynecol, Changhua 50006, Taiwan
[8] Natl Chung Hsing Univ, PhD Programs Translat Med, Taichung 40227, Taiwan
[9] Northwestern Univ, Med Ctr, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA
[10] Chung Yuan Christian Univ, Dept Biomed Engn, Taoyuan 32023, Taiwan
[11] Cent Taiwan Univ Sci & Technol, Dept Med Lab Sci & Biotechnol, Taichung 40601, Taiwan
[12] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei 10041, Taiwan
[13] Natl Taiwan Univ, Coll Med, Dept Obstet & Gynecol, Taipei 10041, Taiwan
[14] Dayeh Univ, Dept Biomed Sci, Changhua 51591, Taiwan
[15] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 30013, Taiwan
关键词
WES; fetal diagnosis; skeletal dysplasia; PPIB; trio analysis; osteogenesis imperfecta; AMINO-ACID SUBSTITUTIONS; OSTEOGENESIS IMPERFECTA; CYCLOPHILIN-B; CONSEQUENCES; PREDICTION; DIAGNOSIS; ISOMERASE;
D O I
10.3390/diagnostics10050286
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Skeletal dysplasia (SD) is a complex group of bone and cartilage disorders often detectable by fetal ultrasound, but the definitive diagnosis remains challenging because the phenotypes are highly variable and often overlap among different disorders. The molecular mechanisms underlying this condition are also diverse. Hundreds of genes are involved in the pathogenesis of SD, but most of them are yet to be elucidated, rendering genotyping almost infeasible except those most common such as fibroblast growth factor receptor 3 (FGFR3), collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), diastrophic dysplasia sulfate transporter (DTDST), and SRY-box 9 (SOX9). Here, we report the use of trio-based whole exome sequencing (trio-WES) with comprehensive gene set analysis in two Taiwanese non-consanguineous families with fetal SD at autopsy. A biparental-origin homozygous c.509G>A(p.G170D) mutation in peptidylprolyl isomerase B (PPIB) gene was identified. The results support a diagnosis of a rare form of autosomal recessive SD, osteogenesis imperfecta type IX (OI IX), and confirm that the use of a trio-WES study is helpful to uncover a genetic explanation for observed fetal anomalies (e.g., SD), especially in cases suggesting autosomal recessive inheritance. Moreover, the finding of an identical PPIB mutation in two non-consanguineous families highlights the possibility of the founder effect, which deserves future investigations in the Taiwanese population.
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页数:13
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