Multiple Developmental Defects in <i>sox11a</i> Mutant Zebrafish with Features of Coffin-Siris Syndrome

Jia, Shaoting; Wu, Xingxing; Wu, Yunya; Cui, Xuefan; Tao, Binbin; Zhu, Zuoyan; Hu, Wei

doi:10.7150/ijbs.47510

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…One limitation of this study is that we were unable to replicate joint contracture in the zebrafish model, which is the most prominent phenotype of LCCS patients. Joint contracture phenotype is generally evaluated in adult zebrafish, 30,31…”

Section: Discussionmentioning

confidence: 99%

ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish

Liu,

Chen,

Zhang

et al. 2023

Clinical Genetics

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The Erb‐B2 receptor tyrosine kinase 3 (ERBB3) gene was first identified as a cause of lethal congenital contracture syndrome (OMIM 607598), while a recent study reported six additional patients carrying ERBB3 variants which exhibited distinct clinical features with evident intestinal dysmotility (OMIM 243180). The potential connection between these phenotypes remains unknown, and the ERBB3‐related phenotype spectrum needs to be better characterized. Here, we described a patient presenting with a multisystemic syndrome including skip segment Hirschsprung disease, bilateral clubfoot deformity, and cardiac defect. Trio‐whole exome sequencing revealed a novel compound heterozygous variant (c.1914‐7C>G; c.2942_2945del) in the patient's ERBB3 gene. RT‐PCR and in vitro minigene analysis demonstrated that variant c.1914‐7C>G caused aberrant mRNA splicing. Both variants resulted in premature termination codon and complete loss of ERBB3 function. erbb3b knockdown in zebrafish simultaneously caused a reduction in enteric neurons in the distal intestine, craniofacial cartilage defects, and micrognathia, which phenotypically mimics ERBB3‐related intestinal dysmotility and some features of lethal congenital contracture syndrome in human patients. These findings provide further patient and animal evidence supporting that ERBB3 deficiency causes a complex syndrome involving multiple systems with phenotypic variability among distinct individuals.

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Section: Discussionmentioning

confidence: 99%

ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish

Liu,

Chen,

Zhang

et al. 2023

Clinical Genetics

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“…SOX11 can facilitate chromatin opening, resulting in nucleolar remodeling and subsequent transcription (Dodonova et al, 2020 ). SOX11 expression is evident in a range of progenitor and stem cells wherein it controls their survival and fate determination in the context of neurogenesis, bone, kidney, and cardiac outflow tract formation (Hyodo‐Miura et al, 2002 ; Jia et al, 2020 ; Kavyanifar et al, 2018 ; Lefebvre, 2019 ; Lefebvre & Bhattaram, 2016 ; Paul et al, 2014 ; Sock et al, 2004 ; Wang et al, 2013 ; Yu et al, 2020 ). SOX11 serves as a transcriptional regulator, and the loss of its functionality can alter downstream target gene expression.…”

Section: Discussionmentioning

confidence: 99%

Two SOX11 variants cause Coffin–Siris syndrome with a new feature of sensorineural hearing loss

Wang

Yang

et al. 2022

American J of Med Genetics Pt A

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Coffin‐Siris syndrome (CSS, OMIM#135900) is a rare congenital disorder associated with neurodevelopmental and dysmorphic features. The primary cause of CSS is pathogenic variants in any of 9 BAF chromatin‐remodeling complex encoding genes or the genes SOX11 and PHF6. Herein, we performed whole‐exome sequencing (WES) and a series of analyses of growth‐related, auditory, and radiological findings in two probands with syndromic sensorineural hearing loss and inner ear malformations who exhibited distinctive facial features, intellectual disability, growth retardation, and fifth finger malformation. Two de novo variants in the SOX11 gene (c.148A>C:p.Lys50Asn; c.811_814del:p.Asn271Serfs*10) were detected in these probands and were identified as pathogenic variants as per ACMG guidelines. These probands were diagnosed as having CSS based upon clinical and genetic findings. This is the first report of CSS caused by variants in SOX11 gene in Chinese individuals. Deleterious SOX11 variants can result in sensorineural hearing loss with inner ear malformation, potentially extending the array of phenotypes associated with these pathogenic variants. We suggest that both genetic and clinical findings be considered when diagnosing syndromic hearing loss.

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“…The length of the fast-twitch fibers was assessed using ImageJ. Phalloidin was previously used to study muscle defects in (Han et al, 2020;Jia et al, 2020;Snow et al, 2008).…”

Section: Phalloidin Staining Of Actin Fibersmentioning

confidence: 99%

Differential impact of dose-range glyphosate on locomotor behavior, neuronal activity, glio-cerebrovascular structures, and transcript regulations in zebrafish larvae

et al. 2021

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Highlights1. In zebrafish larvae, behavioral and brain electrophysiological defects elicit at high glyphosate concentrations.2. Neurological outcomes are not associated with structural neuro-vascular or muscular malformations.3. Morphological signs of microglia activation are reported after exposure to low and high glyphosate concentrations.4. Transcriptomic analysis reveals the deregulation of candidate pathways, possibly extending to neuronal vulnerability.

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Multiple Developmental Defects in sox11a Mutant Zebrafish with Features of Coffin-Siris Syndrome

Cited by 9 publications

References 24 publications

ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish

ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish

Two SOX11 variants cause Coffin–Siris syndrome with a new feature of sensorineural hearing loss

Differential impact of dose-range glyphosate on locomotor behavior, neuronal activity, glio-cerebrovascular structures, and transcript regulations in zebrafish larvae

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