Dataset Information

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

ABSTRACT:

Purpose

We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis.

Methods

We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes.

Results

These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes.

Conclusion

These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

SUBMITTER: Harris HK

PROVIDER: S-EPMC9472083 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

Harris Holly K HK Nakayama Tojo T Lai Jenny J Zhao Boxun B Argyrou Nikoleta N Gubbels Cynthia S CS Soucy Aubrie A Genetti Casie A CA Suslovitch Victoria V Rodan Lance H LH Tiller George E GE Lesca Gaetan G Gripp Karen W KW Asadollahi Reza R Hamosh Ada A Applegate Carolyn D CD Turnpenny Peter D PD Simon Marleen E H MEH Volker-Touw Catharina M L CML Gassen Koen L I van KLIV Binsbergen Ellen van EV Pfundt Rolph R Gardeitchik Thatjana T Vries Bert B A de BBA Immken LaDonna L LL Buchanan Catherine C Willing Marcia M Toler Tomi L TL Fassi Emily E Baker Laura L Vansenne Fleur F Wang Xiadong X Ambrus Julian L JL Fannemel Madeleine M Posey Jennifer E JE Agolini Emanuele E Novelli Antonio A Rauch Anita A Boonsawat Paranchai P Fagerberg Christina R CR Larsen Martin J MJ Kibaek Maria M Labalme Audrey A Poisson Alice A Payne Katelyn K KK Walsh Laurence E LE Aldinger Kimberly A KA Balciuniene Jorune J Skraban Cara C Gray Christopher C Murrell Jill J Bupp Caleb P CP Pascolini Giulia G Grammatico Paola P Broly Martin M Küry Sébastien S Nizon Mathilde M Rasool Iqra Ghulam IG Zahoor Muhammad Yasir MY Kraus Cornelia C Reis André A Iqbal Muhammad M Uguen Kevin K Audebert-Bellanger Severine S Ferec Claude C Redon Sylvia S Baker Janice J Wu Yunhong Y Zampino Guiseppe G Syrbe Steffan S Brosse Ines I Jamra Rami Abou RA Dobyns William B WB Cohen Lilian L LL Blomhoff Anne A Mignot Cyril C Keren Boris B Courtin Thomas T Agrawal Pankaj B PB Beggs Alan H AH Yu Timothy W TW

Genetics in medicine : official journal of the American College of Medical Genetics 20210303 6

<h4>Purpose</h4>We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis.<h4>Methods</h4>We assembled a cohort of 38 individuals (from 33 unrelated famil ...[more]

PMID: 33658631

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Dataset Information

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

Purpose

Methods

Results

Conclusion

Publications

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

Similar Datasets

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