Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy
Abstract Background Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a S...
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Wiley
2020-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1524 |
| _version_ | 1797301262401667072 |
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| author | Xinyue Zhang Yanqin You Xiaoxiao Xie Hong Xu Honghui Zhou Yuanmei Lei Pei Sun Yuanguang Meng Longxia Wang Yanping Lu |
| author_facet | Xinyue Zhang Yanqin You Xiaoxiao Xie Hong Xu Honghui Zhou Yuanmei Lei Pei Sun Yuanguang Meng Longxia Wang Yanping Lu |
| author_sort | Xinyue Zhang |
| collection | DOAJ |
| description | Abstract Background Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short‐rib polydactyly syndrome (SRPS)‐like phenotype. Method Karyotyping and NGS‐based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole‐exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family. Results No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS‐like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short‐rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family. Conclusion Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling. |
| first_indexed | 2024-03-07T23:19:00Z |
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| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:19:00Z |
| publishDate | 2020-12-01 |
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| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-751e50f4a36543bea2db11051f3429212024-02-21T08:38:03ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-12-01812n/an/a10.1002/mgg3.1524Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathyXinyue Zhang0Yanqin You1Xiaoxiao Xie2Hong Xu3Honghui Zhou4Yuanmei Lei5Pei Sun6Yuanguang Meng7Longxia Wang8Yanping Lu9Department of Obstetrics and Gynecology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Obstetrics and Gynecology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Obstetrics and Gynecology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Ultrasound 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Obstetrics and Gynecology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Dermatology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaBeijing Genomics institution Beijing ChinaDepartment of Obstetrics and Gynecology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Ultrasound 1st Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Obstetrics and Gynecology 1st Medical Center of Chinese PLA General Hospital Beijing ChinaAbstract Background Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short‐rib polydactyly syndrome (SRPS)‐like phenotype. Method Karyotyping and NGS‐based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole‐exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family. Results No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS‐like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short‐rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family. Conclusion Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling.https://doi.org/10.1002/mgg3.1524DYNC2LI1short‐rib thoracic dysplasia 15 with polydactyly (SRTD15)skeletal ciliopathywhole‐exome sequencing |
| spellingShingle | Xinyue Zhang Yanqin You Xiaoxiao Xie Hong Xu Honghui Zhou Yuanmei Lei Pei Sun Yuanguang Meng Longxia Wang Yanping Lu Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy Molecular Genetics & Genomic Medicine DYNC2LI1 short‐rib thoracic dysplasia 15 with polydactyly (SRTD15) skeletal ciliopathy whole‐exome sequencing |
| title | Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy |
| title_full | Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy |
| title_fullStr | Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy |
| title_full_unstemmed | Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy |
| title_short | Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy |
| title_sort | whole exome sequencing identified two novel mutations of dync2li1 in fetal skeletal ciliopathy |
| topic | DYNC2LI1 short‐rib thoracic dysplasia 15 with polydactyly (SRTD15) skeletal ciliopathy whole‐exome sequencing |
| url | https://doi.org/10.1002/mgg3.1524 |
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