CASZ1 loss-of-function mutation associated with congenital heart disease

Huang, Ri Tai; Xue, Song; Wang, Juan; Gu, Jian Yun; Xu, Jia Hong; Li, Yan Jie; Li, Ning; Xiao-mi, Yang; Liu, Hua; Zhang, Xiao Dong; Qu, Xin; Xu, Ying; Qiu, Xing Biao; Li, Ruo Gu; Yang, Youwei

doi:10.1016/j.gene.2016.09.044

Cited by 31 publications

(29 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We demonstrate that one mechanism by which CASZ1 is dysregulated in ERMS is through RAS-MEK signaling. Recent studies show that somatic mutations of CASZ1 are significantly enriched in HPV-positive oral cancers 40,41 , and CASZ1 loss-of-function mutations are associated with heart disease 42,43 , which indicates that genetic alterations in CASZ1 are implicated in different types of diseases. With a limited number of patient RMS samples, we observed a loss-of-function genetic alteration in the CASZ1 gene that contributes to the inactivation of CASZ1 transcriptional activities.…”

Section: Discussionmentioning

confidence: 99%

CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG

et al. 2020

View full text Add to dashboard Cite

Embryonal rhabdomyosarcoma (ERMS) is a childhood cancer that expresses myogenic master regulatory factor MYOD but fails to differentiate. Here, we show that the zinc finger transcription factor CASZ1 up-regulates MYOD signature genes and induces skeletal muscle differentiation in normal myoblasts and ERMS. The oncogenic activation of the RAS-MEK pathway suppresses CASZ1 expression in ERMS. ChIP-seq, ATAC-seq and RNA-seq experiments reveal that CASZ1 directly up-regulates skeletal muscle genes and represses non-muscle genes through affecting regional epigenetic modifications, chromatin accessibility and super-enhancer establishment. Next generation sequencing of primary RMS tumors identified a single nucleotide variant in the CASZ1 coding region that potentially contributes to ERMS tumorigenesis. Taken together, loss of CASZ1 activity, due to RAS-MEK signaling or genetic alteration, impairs ERMS differentiation, contributing to RMS tumorigenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Mutations in other several genes have been reported to be associated with congenital heart diseases. These genes include the following: ankyrin repeat domain 1 (ANKRD1) associated with septal defects, NR2F2 gene associated with double outlet ventricle, HAND2 gene associated with familial ventral septal defect, pulmonary stenosis, double outlet right ventricle, tetralogy of Fallot, and CASZ1 gene associated with the ventral septal defects [112][113][114][115][116].…”

Section: Embryogenesis Of the Heartmentioning

confidence: 99%

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Suluba

Liu

Xia

et al. 2020

Egypt J Med Hum Genet

View full text Add to dashboard Cite

Background: Congenital heart diseases (CHDs) are the most common congenital anomalies with an estimated prevalence of 8 in 1000 live births. CHDs occur as a result of abnormal embryogenesis of the heart. Congenital heart diseases are associated with significant mortality and morbidity. The damage of the heart is irreversible due to a lack of regeneration potential, and usually, the patients may require surgical intervention. Studying the developmental biology of the heart is essential not only in understanding the mechanisms and pathogenesis of congenital heart diseases but also in providing us with insight towards developing new preventive and treatment methods. Main body: The etiology of congenital heart diseases is still elusive. Both genetic and environmental factors have been implicated to play a role in the pathogenesis of the diseases. Recently, cardiac transcription factors, cardiacspecific genes, and signaling pathways, which are responsible for early cardiac morphogenesis have been extensively studied in both human and animal experiments but leave much to be desired. The discovery of novel genetic methods such as next generation sequencing and chromosomal microarrays have led to further study the genes, non-coding RNAs and subtle chromosomal changes, elucidating their implications to the etiology of congenital heart diseases. Studies have also implicated non-hereditary risk factors such as rubella infection, teratogens, maternal age, diabetes mellitus, and abnormal hemodynamics in causing CHDs. These etiological factors raise questions on multifactorial etiology of CHDs. It is therefore important to endeavor in research based on finding the causes of CHDs. Finding causative factors will enable us to plan intervention strategies and mitigate the consequences associated with CHDs. This review, therefore, puts forward the genetic and non-genetic causes of congenital heart diseases. Besides, it discusses crucial signaling pathways which are involved in early cardiac morphogenesis. Consequently, we aim to consolidate our knowledge on multifactorial causes of CHDs so as to pave a way for further research regarding CHDs. Conclusion: The multifactorial etiology of congenital heart diseases gives us a challenge to explicitly establishing specific causative factors and therefore plan intervention strategies. More well-designed studies and the use of novel genetic technologies could be the way through the discovery of etiological factors implicated in the pathogenesis of congenital heart diseases.

show abstract

“…20 Further, a heterozygous pathogenic variant in CASZ1 previously has been associated with familial cardiac disease in an autosomal-dominant manner. 21 Family 7. This premature neonate died from a complex CHD (pulmonary stenosis, VSD, over-riding aorta) and was syndromic, with skeletal abnormalities (bilateral tibial hemimelia, clinodactyly, and fifth finger phalangeal hypoplasia; Table 1).…”

Section: Nonphenotype List-directed Analysismentioning

confidence: 99%

Application of Whole Genome Sequencing Technology in the Investigation of Genetic Causes of Fetal, Perinatal, and Early Infant Death

et al. 2017

View full text Add to dashboard Cite

Death in the fetal, perinatal, and early infant age-group has a multitude of causes, a proportion of which is presumed to be genetic. Defining a specific genetic aberration leading to the death is problematic at this young age, due to limited phenotype-genotype correlation inherent in the underdeveloped phenotype, the inability to assess certain phenotypic traits after death, and the problems of dealing with rare disorders. In this study, our aim was to increase the yield of identification of a defined genetic cause of an early death. Therefore, we employed whole genome sequencing and bioinformatic filtering techniques as a comprehensive, unbiased genetic investigation into 16 fetal, perinatal, and early infant deaths, which had undergone a full autopsy. A likely genetic cause was identified in two cases (in genes; COL2A1 and RYR1) and a speculative genetic cause in a further six cases (in genes: ARHGAP35, BBS7, CASZ1, CRIM1, DHCR7, HADHB, HAPLN3, HSPG2, MYO18B, and SRGAP2). This investigation indicates that whole genome sequencing is a significantly enabling technology when determining genetic causes of early death.

show abstract

CASZ1 loss-of-function mutation associated with congenital heart disease

Cited by 31 publications

References 58 publications

CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG

CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Application of Whole Genome Sequencing Technology in the Investigation of Genetic Causes of Fetal, Perinatal, and Early Infant Death

Contact Info

Product

Resources

About