A novel heterozygous missense mutation G316D of SIX3 gene in a Brazilian patient with holoprosencephaly-like phenotype and Langerhans cell histiocytosis

Ribeiro, Lucilene Arilho; Bertolacini, Claudia Danielli Pereira; Quiezi, Rodrigo Gonçalves; Richieri-Costa, Antônio

doi:10.1097/mcd.0b013e32834116ae

Cited by 2 publications

(2 citation statements)

References 5 publications

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“…nsSNV impact predictions may be used to distinguish the most deleterious nsSNVs from those that are merely in strong linkage disequilibrium with a causative nsSNV, 157 or identify deleterious rare nsSNVs that occur on genes that are associated with the disease. [158][159][160] Identifying genes that cause diseases Another use of impact predictors is to discover genes associated with genetic disorders. 161 In these studies, exome sequencing of unrelated patients with the disorder is conducted under the hypothesis that these exomes will be enriched in mutations that impact the function of a causative gene.…”

Section: Guided Mutagenesismentioning

confidence: 99%

Single nucleotide variations: Biological impact and theoretical interpretation

Koire²,

et al. 2014

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Genome-wide association studies (GWAS) and whole-exome sequencing (WES) generate massive amounts of genomic variant information, and a major challenge is to identify which variations drive disease or contribute to phenotypic traits. Because the majority of known disease-causing mutations are exonic non-synonymous single nucleotide variations (nsSNVs), most studies focus on whether these nsSNVs affect protein function. Computational studies show that the impact of nsSNVs on protein function reflects sequence homology and structural information and predict the impact through statistical methods, machine learning techniques, or models of protein evolution. Here, we review impact prediction methods and discuss their underlying principles, their advantages and limitations, and how they compare to and complement one another. Finally, we present current applications and future directions for these methods in biological research and medical genetics.

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Section: Guided Mutagenesismentioning

confidence: 99%

Single nucleotide variations: Biological impact and theoretical interpretation

Koire²,

et al. 2014

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“…Mutations in SIX3 in humans are associated with holoprosencephaly (Wallis et al, 1999;Lacbawan et al, 2009;Solomon et al, 2009;Ribeiro et al, 2011). Holoprosencephaly (HPE) is a cephalic disorder of varying severity that results when the embryonic forebrain fails to separate properly.…”

Section: Vsx2 (Chx10)mentioning

confidence: 99%

The Role of Rx in Embryonic Retinogenesis: Determining Genetic Influences on Optic Vesicle Formation and Photoreceptor Cell Fate

Rodgers¹

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Eye development is a dynamic and complex process that is controlled by the interactions of transcription factors, signaling pathways, and growth factors. Disruption of the developmental process can result in ocular malformations or retinal diseases, which can cause blindness. Developing tools to study embryonic retinogenesis and understanding the molecular mechanisms involved are important for increasing our understanding of neural development, understanding ocular malformations such as anophthalmia, and may improve or lead to new treatments for eye diseases including blindness. This work aims to develop new tools for studying early eye development and explore genes associated with optic vesicle development and photoreceptor cell fate. In Study 1, we sought to identify and characterize markers of embryonic cone photoreceptors. We identified that two genes involved in phototransduction, phosducin and cone transducin , are expressed in developing cones. We characterized the temporal and spatial profile of both genes and their associated proteins over the developmental timeline of retinogenesis. Further, we determined their colocalization with known cone and photoreceptor markers and thus established them as useful markers for further studies of early cone histogenesis. In Study 2, we assessed the role of the homeobox gene, Rx, in progenitor proliferation and cell fate determination in the mouse retina using a conditional knockout. Deletion of Rx in retinal progenitors led to a loss of retinal lamination, depletion of the retinal progenitors and in the mature retina showed changes in retinal cell types. Late-born cells (rods, bipolar cells, and Müller glia) were absent, likely due to the depleted progenitor pool. Cones (an early-born retinal cell type) were also absent; examination of cone histogenesis showed Rx is necessary for cone photoreceptor generation. Finally, in Study 3 we identified an effective gene knockdown method for 3D optic vesicle organoid culture that is useful for studying gene expression and early retinal development. Using this method, we assessed the roles of three candidate genes in optic vesicle development and identified one gene that warrants further investigation in vivo. Collectively these studies provide new tools for studying early embryogenesis and further our knowledge of the genetics underlying optic vesicle development and cone photoreceptor formation. iii Dedication This dissertation is dedicated to my parents, William and Bernice Rodgers. Who I am today, and what I have accomplished are all due to having remarkable, loving and supportive parents. Your love, encouragement and prayers over the years made completing this dissertation possible.

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A novel heterozygous missense mutation G316D of SIX3 gene in a Brazilian patient with holoprosencephaly-like phenotype and Langerhans cell histiocytosis

Cited by 2 publications

References 5 publications

Single nucleotide variations: Biological impact and theoretical interpretation

Single nucleotide variations: Biological impact and theoretical interpretation

The Role of Rx in Embryonic Retinogenesis: Determining Genetic Influences on Optic Vesicle Formation and Photoreceptor Cell Fate

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