Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development

Tischfield, Max A.; Bosley, Thomas M.; Salih, Mustafa A.; Alorainy, Ibrahim A.; Şener, Emin Cumhur; Nester, Michael; Oystreck, Darren T.; Chan, Wai Man; Andrews, Caroline; Erickson, Robert P.; Engle, Elizabeth C.

doi:10.1038/ng1636

Cited by 278 publications

(252 citation statements)

References 15 publications

Supporting

Mentioning

248

Contrasting

Unclassified

Order By: Relevance

“…263,264 A HOXA1-related disorder, Bosley-Salih -Alorainy syndrome, has been identified in a small patient sample, with symptoms that include delayed maturation and autism. 265 Gene expression profiles in normal and Hoxa1 À/À embryonic stem cells have shown that Hoxa1 regulates expression of Bdnf and other genes important for development. 266 Stodgell et al 254 have shown that, in rats, prenatal exposure to valproic acid leads to marked increases in embryonic Hoxa1 expression, possibly through the inhibition of histone deacetylases.…”

Section: Mouse Models Of Environmental Contributions To Autism Etiologymentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

View full text Add to dashboard Cite

Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

show abstract

Section: Mouse Models Of Environmental Contributions To Autism Etiologymentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

View full text Add to dashboard Cite

show abstract

“…Highthroughput molecular genetics has changed the face of medical research dramatically, but it has perhaps had less of an impact on clinical medicine than one might expect [Tischfield et al, 2005]. For example, it is technically feasible to use gene-chip methodology to screen for any of several hundred possible mutations that cause cystic fibrosis [Schrijver et al, 2005].…”

Section: Clinical and Economic Aspects Of Mutation Detectionmentioning

confidence: 99%

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Wyrobek

Mulvihill

Wassom

et al. 2007

Environ and Mol Mutagen

View full text Add to dashboard Cite

Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ~5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multipleendpoint studies. Additional studies could involve the examination of transgenerational effects NIH Public AccessAuthor Manuscript Environ Mol Mutagen. Author manuscript; available in PMC 2007 November 8. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germcell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis.

show abstract

“…В качестве примера можно привести гомозиготную мутацию в гене HOXA1, которая ассоциирована с синдромами BosleySalih-Alorainy, дискинетическим синдромом Атабаски [35]. Интересен факт, что тяжелые пороки развития сердечно-сосудистой системы (тетрада Фалло, ДАК, дефект межжелудочковой перегородки и др.)…”

Section: генетикаunclassified

Aortopathy pathophysiology features in patients with bicuspid aortic valve.

et al. 2016

View full text Add to dashboard Cite

This review is devoted to one of the vital topics in cardiovascular surgery -pathophysiologyof an aortopathy in case of bicuspid aortic valve. In the article reviewed the modern point of view on a problem considering new achievements in genetics, molecular biology and altered haemodynamic.Key words: aortic aneurysm-bicuspid aortic valve-metalloproteinase. ТұжырымдамаӘдебиетке болжамдалған шолу қантамырлық-жүрек хирургиясының өзекті тақырыптарының бірі -екі жақтаулы аорталық қақпашасы бар пациенттерде патофизиологиялық аортопатияның ерекшеліктеріне арналған. Мақалада генетикадағы, молекулярлық биологиядағы, гемодинамика патологиясындағы жаңа жетістіктер ескеріле отырып, проблемаға заманауи тұрғыдағы көзқарас берілен.Маңызды сөздер: аорта аневризмі -екі жақтаулы аорталық қақпаша -металлопротеиназдар.оСоБенноСти патофизиологии аортопатии у пациентов С двуСтворчатыМ аортальныМ клапаноМ. Сейдалин а.о. 1 ,туганбеков т.у. 2 , диколаев в.д. 2,3, айталиев С.е 3 .1 «Городской кардиологический центр», отделение кардиохирургии, Алматы, Казахстан 2 «Медицинский Университет Астана», кафедра хирургии, Астана, Казахстан 3«Национальный научный медицинский центр», отделение кардиохирургии, Астана, Казахстан Резюме.Предполагаемый обзор литературы посвящен одной из актуальных тем в сердечно-сосудистой хирургии -патофизиологии аортопатии при двустворчатом аортальном клапане. В статье дан современный взгляд на проблему с учетом новых достижений в генетике, молекулярной биологии, патологии гемодинамики.Ключевые слова: аневризма аорты -двустворчатый аортальный клапан -металлопротеиназы.

show abstract

Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development

Cited by 278 publications

References 15 publications

Advances in behavioral genetics: mouse models of autism

Advances in behavioral genetics: mouse models of autism

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Aortopathy pathophysiology features in patients with bicuspid aortic valve.

Contact Info

Product

Resources

About