Combined exome sequencing and deep phenotyping in highly selected fetuses with skeletal dysplasia during the first and second trimesters improves diagnostic yield
| Autor: | H. Xu, Yuan Ren, Zhiying Gao, Qingdong Zhao, Honghui Zhou, Rui Song, Pei Sun, Manli Zhang, Xinyue Zhang, Longxia Wang, Yanping Lu, Xiaoxiao Xie, Yuanguang Meng, Yanqin You |
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| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Adult Pathology medicine.medical_specialty Gestational Age 030105 genetics & heredity Compound heterozygosity Osteochondrodysplasias Genetic analysis Ultrasonography Prenatal 03 medical and health sciences Prenatal ultrasound 0302 clinical medicine Fetus Dentinogenesis Imperfecta Pregnancy Exome Sequencing Medicine Humans FLNB Genetics (clinical) Exome sequencing 030219 obstetrics & reproductive medicine business.industry Obstetrics and Gynecology medicine.disease Phenotype Pregnancy Trimester First Dysplasia Pregnancy Trimester Second embryonic structures Female business |
| Zdroj: | Prenatal diagnosisREFERENCES. 41(11) |
| ISSN: | 1097-0223 |
| Popis: | Objective To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES). Method Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. The affected families underwent multiplatform genetic tests. Results Of the 27 affected fetuses, 21 (77.8%) had pathogenic or potential pathogenic variations in the following genes: COL1A1, FGFR3, COL2A1, COL1A2, FLNB, DYNC2LI1, and TRIP11. Two fetuses had compound heterozygous mutations in DYNC2LI1 and TRIP11, respectively, and the other 19 carried de novo autosomal dominant variants. Novel variants were identified in COL1A1, COL2A1, COL1A2, DYNC2LI1, and TRIP11 in 11 fetuses. We also included the first description of the phenotype of odontochondrodysplasia in a prenatal setting. Conclusions ES or panel sequencing offers a high diagnostic yield for fetal skeletal dysplasia during the first and second trimesters. Comprehensive and complete phenotypic information is indispensable for genetic analysis and the expansion of genotype-phenotype correlations in fetal skeletal abnormalities. |
| Databáze: | OpenAIRE |
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