The chromatin remodeler chd5 is necessary for proper head development during embryogenesis of Danio rerio

Bishop, Brett; Ho, Kwok Ki; Tyler, Kim; Smith, Amanda R.; Bonilla, Sylvia; Leung, Yiu-Wing; Ogas, Joe

doi:10.1016/j.bbagrm.2015.06.006

Cited by 10 publications

(7 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 16 out of the 25 patients with unknown microcephaly and CNV findings (Table 1b) we identified genes which could potentially play a significant role in small head circumference. From a total of 21 candidate genes, only 6 (FREM1, SOX1, ARHGEF7, EHMT1, CHD5, RE(RE)) have been previously reported to be involved in brain deficit causing microcephaly (Table 1b and Table 2) (8)(9)(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly

et al. 2017

View full text Add to dashboard Cite

BackroundMicrocephaly can either be isolated or it may coexist with other neurological entities and/or multiple congenital anomalies, known as syndromic microcephaly. Although many syndromic cases can be classified based on the characteristic phenotype, some others remain uncertain and require further investigation. The present study describes the application of array-comparative genomic hybridization (array-CGH) as a diagnostic tool for the study of patients with clinically unknown syndromic microcephaly.MethodsFrom a cohort of 210 unrelated patients referred with syndromic microcephaly, we applied array-CGH analysis in 53 undiagnosed cases. In all the 53 cases except one, previous standard karyotype was negative. High-resolution 4 × 180K and 1 × 244K Agilent arrays were used in this study.ResultsIn 25 out of the 53 patients with microcephaly among other phenotypic anomalies, array-CGH revealed copy number variations (CNVs) ranging in size between 15 kb and 31.6 Mb. The identified CNVs were definitely causal for microcephaly in 11/53, probably causal in 7/53, and not causal for microcephaly in 7/53 patients. Genes potentially contributing to brain deficit were revealed in 16/53 patients.ConclusionsArray-CGH contributes to the elucidation of undefined syndromic microcephalic cases by permitting the discovery of novel microdeletions and/or microduplications. It also allows a more precise genotype-phenotype correlation by the accurate definition of the breakpoints in the deleted/duplicated regions.

show abstract

Section: Discussionmentioning

confidence: 99%

Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, zebrafish chd7 mutants display microphthalmia, suggesting that loss of Chd7 does have negative consequences even at early stages of zebrafish eye development. Alternatively, there may be another Chd family member (such as Chd5, which is expressed in the eye) that can compensate for the loss of Chd7 in zebrafish with respect to optic fissure fusion (Bishop et al, 2015;El-Brolosy et al, 2019). It is also possible that the molecular mechanism of choroid fissure closure is different between species, with Chd7 being required for certain steps of this process in the mouse but not in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length

Krueger

Bills

Lim

et al. 2022

Preprint

View full text Add to dashboard Cite

Mutations in the chromatin remodeling factor CHD7 are the predominant cause of CHARGE syndrome, a congenital disorder that frequently includes ocular coloboma. Although CHD7 is known to be required for proper ocular morphogenesis, its role in retinal development has not been thoroughly investigated. Given that individuals with CHARGE syndrome can experience visual impairment even in the absence of coloboma, a better understanding of CHD7 function in the retina is needed. In this study, we characterized the expression pattern of Chd7 in the developing zebrafish and mouse retina and documented ocular and retinal phenotypes in Chd7 loss-of-function mutants. Zebrafish Chd7 was expressed throughout the retinal neuroepithelium when retinal progenitor cells were actively proliferating, and later in subsets of newly post-mitotic retinal cells. At stages of retinal development when most retinal cell types had terminally differentiated, Chd7 expression remained strong in the ganglion cell layer and in some cells in the inner nuclear layer. Intriguingly, strong expression of Chd7 was also observed in the outer nuclear layer where it was co-expressed with markers of post-mitotic cone and rod photoreceptors. Expression of mouse CHD7 displayed a similar pattern, including expression in the ganglion cells, subsets of inner nuclear layer cells, and in the distal outer nuclear layer as late as P15. Two different mutant chd7 zebrafish lines were characterized for ocular and retinal defects. These mutants displayed microphthalmia, reduced numbers of cone photoreceptors, and truncated rod and cone photoreceptor outer segments. Reduced cone photoreceptor number and abnormal outer segments were also observed in heterozygous Chd7 mutant mice. Taken together, our results in zebrafish and mouse reveal a conserved, previously undescribed role for Chd7 in retinal development and photoreceptor outer segment morphogenesis. Moreover, our work suggests an avenue of future investigation into the pathogenesis of visual system defects in CHARGE syndrome.

show abstract

“…Since the nonsense variant affects only a single transcript (out of several known isoforms) and the missense variant has weak predictions, the significance of these variants is unclear. The brothers also shared a heterozygous missense variant in CDH5 , whose knockdown has been associated with reduced head and eye size in zebrafish [ 22 ]; however, this variant was inherited from the unaffected father.…”

Section: Discussionmentioning

confidence: 99%

Novel Genetic Diagnoses in Septo-Optic Dysplasia

Reis

Seese²,

Maheshwari³

et al. 2022

Genes

View full text Add to dashboard Cite

Septo-optic dysplasia (SOD) is a developmental phenotype characterized by midline neuroradiological anomalies, optic nerve hypoplasia, and pituitary anomalies, with a high degree of variability and additional systemic anomalies present in some cases. While disruption of several transcription factors has been identified in SOD cohorts, most cases lack a genetic diagnosis, with multifactorial risk factors being thought to play a role. Exome sequencing in a cohort of families with a clinical diagnosis of SOD identified a genetic diagnosis in 3/6 families, de novo variants in SOX2, SHH, and ARID1A, and explored variants of uncertain significance in the remaining three. The outcome of this study suggests that investigation for a genetic etiology is warranted in individuals with SOD, particularly in the presence of additional syndromic anomalies and when born to older, multigravida mothers. The identification of causative variants in SHH and ARID1A further expands the phenotypic spectra associated with these genes and reveals novel pathways to explore in septo-optic dysplasia.

show abstract

The chromatin remodeler chd5 is necessary for proper head development during embryogenesis of Danio rerio

Cited by 10 publications

References 90 publications

Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly

Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly

Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length

Novel Genetic Diagnoses in Septo-Optic Dysplasia

Contact Info

Product

Resources

About