An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families
Abstract Primary ciliary dyskinesia (PCD) is clinically characterized by neonatal respiratory distress, chronic sinusitis, bronchiectasis and infertility, and situs inversus in 50% of the patients. PCD is a result of mutations in genes encoding proteins involved in ciliary function, and is primarily...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-08510-z |
| _version_ | 1818851605907243008 |
|---|---|
| author | Ting Guo Zhi-Ping Tan Hua-Mei Chen Dong-yuan Zheng Lv liu Xin-Gang Huang Ping Chen Hong Luo Yi-Feng Yang |
| author_facet | Ting Guo Zhi-Ping Tan Hua-Mei Chen Dong-yuan Zheng Lv liu Xin-Gang Huang Ping Chen Hong Luo Yi-Feng Yang |
| author_sort | Ting Guo |
| collection | DOAJ |
| description | Abstract Primary ciliary dyskinesia (PCD) is clinically characterized by neonatal respiratory distress, chronic sinusitis, bronchiectasis and infertility, and situs inversus in 50% of the patients. PCD is a result of mutations in genes encoding proteins involved in ciliary function, and is primarily inherited in an autosomal recessive fashion. Diagnosis of PCD is often a challenging task due to its high clinical and genetic heterogeneities. In the present study, we attempted to use whole-exome sequencing (WES) combined with runs of homozygosity (ROH) approaches to identify the genetic defects in four Chinese consanguineous families with clinical PCD. We successfully identified three recently acknowledged PCD genes: DYX1C1, CCNO and ARMC4, and one well-characterized PCD gene, DNAI1. Our study provides compelling evidence that WES in combination with ROH analysis is an efficient diagnostic tool for identifying genetic causes of PCD in consanguineous families. Furthermore, our work expands the genetic mutation spectrum in PCD, and provides the additional tools to better serve the counseling of the families with PCD. |
| first_indexed | 2024-12-19T07:07:41Z |
| format | Article |
| id | doaj.art-d90d30b19c3640d1b931af597747914b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T07:07:41Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d90d30b19c3640d1b931af597747914b2022-12-21T20:31:15ZengNature PortfolioScientific Reports2045-23222017-08-01711710.1038/s41598-017-08510-zAn effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous familiesTing Guo0Zhi-Ping Tan1Hua-Mei Chen2Dong-yuan Zheng3Lv liu4Xin-Gang Huang5Ping Chen6Hong Luo7Yi-Feng Yang8Department of Respiratory Medicine, the Second Xiangya Hospital, Central South UniversityCentral South University Center for Clinical Gene Diagnosis and Treatment, the Second Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, Chang Sha Central HospitalDepartment of Respiratory Medicine, the Second Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, the Second Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, the Second Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, the Second Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, the Second Xiangya Hospital, Central South UniversityCentral South University Center for Clinical Gene Diagnosis and Treatment, the Second Xiangya Hospital, Central South UniversityAbstract Primary ciliary dyskinesia (PCD) is clinically characterized by neonatal respiratory distress, chronic sinusitis, bronchiectasis and infertility, and situs inversus in 50% of the patients. PCD is a result of mutations in genes encoding proteins involved in ciliary function, and is primarily inherited in an autosomal recessive fashion. Diagnosis of PCD is often a challenging task due to its high clinical and genetic heterogeneities. In the present study, we attempted to use whole-exome sequencing (WES) combined with runs of homozygosity (ROH) approaches to identify the genetic defects in four Chinese consanguineous families with clinical PCD. We successfully identified three recently acknowledged PCD genes: DYX1C1, CCNO and ARMC4, and one well-characterized PCD gene, DNAI1. Our study provides compelling evidence that WES in combination with ROH analysis is an efficient diagnostic tool for identifying genetic causes of PCD in consanguineous families. Furthermore, our work expands the genetic mutation spectrum in PCD, and provides the additional tools to better serve the counseling of the families with PCD.https://doi.org/10.1038/s41598-017-08510-z |
| spellingShingle | Ting Guo Zhi-Ping Tan Hua-Mei Chen Dong-yuan Zheng Lv liu Xin-Gang Huang Ping Chen Hong Luo Yi-Feng Yang An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families Scientific Reports |
| title | An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families |
| title_full | An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families |
| title_fullStr | An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families |
| title_full_unstemmed | An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families |
| title_short | An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families |
| title_sort | effective combination of whole exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families |
| url | https://doi.org/10.1038/s41598-017-08510-z |
| work_keys_str_mv | AT tingguo aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT zhipingtan aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT huameichen aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT dongyuanzheng aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT lvliu aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT xinganghuang aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT pingchen aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT hongluo aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT yifengyang aneffectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT tingguo effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT zhipingtan effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT huameichen effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT dongyuanzheng effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT lvliu effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT xinganghuang effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT pingchen effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT hongluo effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies AT yifengyang effectivecombinationofwholeexomesequencingandrunsofhomozygosityforthediagnosisofprimaryciliarydyskinesiainconsanguineousfamilies |