A novel compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome.

IF 2.7 3区 生物学
Sujie Xiong, Guangyao Hu, Yao Zhou, Fei Sun, Yanlin Ma
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引用次数: 0

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.

中国Jeune综合征家族DYNC2H1基因的一种新的复合杂合突变。
背景:动力蛋白细胞质双重链1 (DYNC2H1)基因编码一个细胞质动力蛋白亚基。细胞质动力蛋白向微管的负端运输货物,因此被称为“逆行”细胞马达。DYNC2H1突变是伴有或不伴有多指畸形(SRTD3)的短胸椎发育不良综合征III型的主要致病突变。早期诊断SRTD3产前超声单独是困难的。在这种情况下,一对夫妇连续生了三个患有SRTD3的婴儿,他们要求生育指导,以避免再生一个患有SRTD3的婴儿。方法:采用全基因组测序(WGS)、常规g带核型分析、荧光定量聚合酶链反应(pcr)、全外显子组测序(WES)等方法,对妊娠19周的羊水进行细胞遗传学和分子遗传学分析。父母外周血样本也通过Sanger测序筛选srtd3相关突变。结果:鉴定出DYNC2H1基因的两个复合杂合突变C . 10594 C . > T和C . 7720g . > A,分别遗传自母亲和父亲。胎儿的母亲是C . 10594 C . > T变异的杂合型,胎儿的父亲是C . 7720g . > A变异的杂合型。突变C . 10594 C . > T是一种无义突变,据信具有致病性,此前已有报道。突变c.7720G . > A是一种错义突变,目前尚未报道。此外,在胎儿中未发现染色体异常或致病性拷贝数变异(CNVs)。患者在PGT-M和IVF-ET后未怀孕。这个家庭随后接受了捐赠的卵子;成功怀孕,生下了一个健康的女孩。结论:DYNC2H1的复合异质突变最终解释了本研究报道的疾病表型的多样性,并可用于指导未来的妊娠。我们的发现扩大了DYNC2H1在这种罕见疾病中的突变谱,并强调了WES在产前适应症不明确的骨骼发育不良诊断中的价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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