1.Family analysis of a child with Short-rib polydactyly syndrome type III due to variant of DYNC2H1 gene.
Haiyue ZHAO ; Leilei LI ; Ruizhi LIU ; Xiao YANG
Chinese Journal of Medical Genetics 2022;39(8):881-883
OBJECTIVE:
To report on the clinical characteristics of a family of short-rib polydactyly syndrome type III and its pathogenic variants.
METHODS:
Muscle samples from the the third fetus was collected after the induction of labor, and peripheral blood samples of its parents and grandparents were also collected. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variants were verified by Sanger sequencing of the family.
RESULTS:
The proband was found to harbor a c.9819+1G>A variant and a c.4625C>A variant of the DYNC2H1 gene, which were respectively inherited from its mother and father. Sanger sequencing verified that the family has fit the autosomal recessive inheritance.
CONCLUSION
The c.9819+1G>A and c.4625C>A variants of the DYNC2H1 gene probably underlay the short-rib polydactyly syndrome type 3 in the proband.
Child
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Cytoplasmic Dyneins/genetics*
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Humans
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Mutation
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Pedigree
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Ribs
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Short Rib-Polydactyly Syndrome/genetics*
2.Clinical feature and pathogenic analysis of a fetus with split hand-foot malformation.
Chuang LI ; Yuan LYU ; Rui HOU ; Caixia LIU ; Jesse LI-LING ; Huan LI
Chinese Journal of Medical Genetics 2020;37(4):462-466
OBJECTIVE:
To analyze the clinical feature of a fetus with split hand-foot malformation (SHFM) and to explore its etiology.
METHODS:
Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed. Genomic copy number variations (CNVs) of the fetus was analyzed by next-generation sequencing (NGS). Its parents were subjected to chromosomal karyotyping, NGS and fluorescence in situ hybridization (FISH) assays. Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs.
RESULTS:
Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a V-shape, which was suggestive of SFHM. The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region. FISH and NGS analysis of both parents were normal. Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene, while the copy numbers of SEM1, DLX5 and DLX6 genes were normal.
CONCLUSION
The 7q21.3 microdeletion probably underlies the SHFM of the fetus, which has a de novo origin.
Chromosome Deletion
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Chromosomes, Human, Pair 7
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genetics
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Cytoplasmic Dyneins
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genetics
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DNA Copy Number Variations
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Fetus
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Humans
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In Situ Hybridization, Fluorescence
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Karyotyping
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Limb Deformities, Congenital
;
genetics
3.Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1.
Chang Jian YANG ; Shuang WANG ; Dan Dan TAN ; Yi Dan LIU ; Yan Bin FAN ; Cui Jie WEI ; Dan Yu SONG ; Ying ZHU ; Hui XIONG
Chinese Journal of Pediatrics 2023;61(2):154-158
Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.
Female
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Male
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Humans
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Intellectual Disability
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Retrospective Studies
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Muscular Atrophy, Spinal/genetics*
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Lower Extremity
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Muscle Weakness
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Muscular Atrophy
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Contracture
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Cytoplasmic Dyneins/genetics*
4.Genetic genes associated with oligospermia, asthenospermia and teratospermia: Advances in studies.
Ke GAO ; Zhi-Qiang WANG ; Xing-Chen LIU ; Zhi-Long DONG ; Wen-Sheng SHAN
National Journal of Andrology 2017;23(4):367-371
Approximately 2,300 genes are found to be associated with spermiogenesis and their expressions play important roles in the regulation of spermiogenesis. In recent years, more and more attention has been focused on the studies of the genes associated with oligospermia, asthenospermia and teratospermia and their molecular mechanisms. Some genes, such as GSTM1, DNMT3L, and CYP1A1, have been shown to be potentially associated with oligospermia; some, such as CATSPER1, CRISP2, SEPT4, TCTE3, TEKT4, and DNAH1, with asthenospermia; and still others, such as DPY19L2 and AURKC, with teratospermia. These findings have provided a molecular basis for the studies of the pathogenesis of oligospermia, asthenospermia and teratospermia, as well as a new approach to the exploration of new diagnostic and therapeutic techniques.
Asthenozoospermia
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genetics
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Aurora Kinase C
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genetics
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Calcium Channels
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genetics
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Cytochrome P-450 CYP1A1
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genetics
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Cytoplasmic Dyneins
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DNA (Cytosine-5-)-Methyltransferases
;
genetics
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Dyneins
;
genetics
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Glutathione Transferase
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genetics
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Glycoproteins
;
genetics
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Humans
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Male
;
Membrane Proteins
;
genetics
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Microtubule Proteins
;
genetics
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Oligospermia
;
genetics
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Spermatogenesis
;
genetics
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Teratozoospermia
;
genetics
5.Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling.
Zhi-Dong LIU ; Su ZHANG ; Jian-Jin HAO ; Tao-Rong XIE ; Jian-Sheng KANG
Protein & Cell 2016;7(9):638-650
Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein malfunction and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracellular signaling pathways that can protect against or delay this pathogenic process. Here, we show that the DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. With this cellular model, we are able to find that activation of RAS-RAF-MEK signaling protects against neuronal atrophy induced by DYNC1I1 deficiency, which relies on MEK-dependent autophagy in neuron. Moreover, we further reveal that BRAF also protects against neuronal atrophy induced by mitochondrial impairment. These findings demonstrate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.
Animals
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Cell Line
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Cytoplasmic Dyneins
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genetics
;
metabolism
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Hippocampus
;
metabolism
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pathology
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MAP Kinase Kinase Kinases
;
genetics
;
metabolism
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MAP Kinase Signaling System
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Mice
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Mice, Knockout
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Neurodegenerative Diseases
;
genetics
;
metabolism
;
pathology
;
Proto-Oncogene Proteins B-raf
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genetics
;
metabolism
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ras Proteins
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genetics
;
metabolism