A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome
Abstract Background The dynein cytoplasmic two heavy chain 1 (DYNC2H1) gene encodes a cytoplasmic dynein subunit. Cytoplasmic dyneins transport cargo towards the minus end of microtubules and are thus termed the “retrograde” cellular motor. Mutations in DYNC2H1 are the main causative mutations of sh...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Hereditas |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41065-025-00375-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571587352592384 |
|---|---|
| author | Sujie Xiong Guangyao Hu Yao Zhou Fei Sun Yanlin Ma |
| author_facet | Sujie Xiong Guangyao Hu Yao Zhou Fei Sun Yanlin Ma |
| author_sort | Sujie Xiong |
| collection | DOAJ |
| description | Abstract Background The dynein cytoplasmic two heavy chain 1 (DYNC2H1) gene encodes a cytoplasmic dynein subunit. Cytoplasmic dyneins transport cargo towards the minus end of microtubules and are thus termed the “retrograde” cellular motor. Mutations in DYNC2H1 are the main causative mutations of short rib-thoracic dysplasia syndrome type III with or without polydactyly (SRTD3). Early diagnosis of SRTD3 prenatally by ultrasound alone is difficult. In this case, a couple who gave birth to three consecutive babies with SRTD3 requested fertility guidance to avoid having another baby with SRTD3. Methods Cytogenetic and molecular genetic analyses of amniotic fluid via whole-genome sequencing (WGS), routine G-banded karyotype analysis, fluorescent quantitative polymerase chain reaction, and whole-exome sequencing (WES) were performed at 19 weeks. Peripheral blood samples from the parents were also screened by Sanger sequencing for SRTD3-related mutations. Results Two compound heterozygous mutations, c.10,594 C > T and c.7720G > A, in the DYNC2H1 gene were identified, which were inherited from the mother and father, respectively. The foetus’s mother is heterozygous for the c.10,594 C > T variant, and the foetus’s father is heterozygous for the c.7720G > A variant. The mutation c.10,594 C > T, which is a nonsense mutation believed to be pathogenic, has been previously reported. The mutation c.7720G > A, which is a missense mutation, has yet to be reported. Moreover, no chromosomal abnormalities or pathogenic copy number variations (CNVs) were detected in the foetus. The patient did not become pregnant after PGT-M and IVF-ET. This family subsequently accepted donated eggs; a successful pregnancy occurred, and a healthy girl was born. Conclusion The compound heterogeneous mutations in DYNC2H1 ultimately accounts for the diversity of disease phenotypes reported in this study and can be used to guide future pregnancies. Our findings expand the mutation spectrum of DYNC2H1 in this rare disease and highlight the value of WES in the diagnosis of skeletal dysplasia with unclear prenatal indications. |
| format | Article |
| id | doaj-art-68d835c0d00a49fab6ebadce06a31db4 |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj-art-68d835c0d00a49fab6ebadce06a31db42025-02-02T12:27:40ZengBMCHereditas1601-52232025-01-0116211810.1186/s41065-025-00375-xA novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndromeSujie Xiong0Guangyao Hu1Yao Zhou2Fei Sun3Yanlin Ma4Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education & Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Provincie & Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityKey Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education & Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Provincie & Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityKey Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education & Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Provincie & Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityKey Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education & Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Provincie & Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityKey Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education & Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Provincie & Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityAbstract Background The dynein cytoplasmic two heavy chain 1 (DYNC2H1) gene encodes a cytoplasmic dynein subunit. Cytoplasmic dyneins transport cargo towards the minus end of microtubules and are thus termed the “retrograde” cellular motor. Mutations in DYNC2H1 are the main causative mutations of short rib-thoracic dysplasia syndrome type III with or without polydactyly (SRTD3). Early diagnosis of SRTD3 prenatally by ultrasound alone is difficult. In this case, a couple who gave birth to three consecutive babies with SRTD3 requested fertility guidance to avoid having another baby with SRTD3. Methods Cytogenetic and molecular genetic analyses of amniotic fluid via whole-genome sequencing (WGS), routine G-banded karyotype analysis, fluorescent quantitative polymerase chain reaction, and whole-exome sequencing (WES) were performed at 19 weeks. Peripheral blood samples from the parents were also screened by Sanger sequencing for SRTD3-related mutations. Results Two compound heterozygous mutations, c.10,594 C > T and c.7720G > A, in the DYNC2H1 gene were identified, which were inherited from the mother and father, respectively. The foetus’s mother is heterozygous for the c.10,594 C > T variant, and the foetus’s father is heterozygous for the c.7720G > A variant. The mutation c.10,594 C > T, which is a nonsense mutation believed to be pathogenic, has been previously reported. The mutation c.7720G > A, which is a missense mutation, has yet to be reported. Moreover, no chromosomal abnormalities or pathogenic copy number variations (CNVs) were detected in the foetus. The patient did not become pregnant after PGT-M and IVF-ET. This family subsequently accepted donated eggs; a successful pregnancy occurred, and a healthy girl was born. Conclusion The compound heterogeneous mutations in DYNC2H1 ultimately accounts for the diversity of disease phenotypes reported in this study and can be used to guide future pregnancies. Our findings expand the mutation spectrum of DYNC2H1 in this rare disease and highlight the value of WES in the diagnosis of skeletal dysplasia with unclear prenatal indications.https://doi.org/10.1186/s41065-025-00375-xShort-rib thoracic dysplasia 3 with or without polydactylyDYNC2H1 geneFoetal growth restrictionWhole-exome sequencing |
| spellingShingle | Sujie Xiong Guangyao Hu Yao Zhou Fei Sun Yanlin Ma A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome Hereditas Short-rib thoracic dysplasia 3 with or without polydactyly DYNC2H1 gene Foetal growth restriction Whole-exome sequencing |
| title | A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome |
| title_full | A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome |
| title_fullStr | A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome |
| title_full_unstemmed | A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome |
| title_short | A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome |
| title_sort | novel compound heterozygous mutation in the dync2h1 gene in a chinese family with jeune syndrome |
| topic | Short-rib thoracic dysplasia 3 with or without polydactyly DYNC2H1 gene Foetal growth restriction Whole-exome sequencing |
| url | https://doi.org/10.1186/s41065-025-00375-x |
| work_keys_str_mv | AT sujiexiong anovelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT guangyaohu anovelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT yaozhou anovelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT feisun anovelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT yanlinma anovelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT sujiexiong novelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT guangyaohu novelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT yaozhou novelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT feisun novelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome AT yanlinma novelcompoundheterozygousmutationinthedync2h1geneinachinesefamilywithjeunesyndrome |