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...

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Main Authors: Sujie Xiong, Guangyao Hu, Yao Zhou, Fei Sun, Yanlin Ma
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Hereditas
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Online Access:https://doi.org/10.1186/s41065-025-00375-x
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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.
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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
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