Journal article

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Francesca Clementina Radio, Kaifang Pang, Andrea Ciolfi, Michael A Levy, Andres Hernandez-Garcia, Lucia Pedace, Francesca Pantaleoni, Zhandong Liu, Elke de Boer, Adam Jackson, Alessandro Bruselles, Haley McConkey, Emilia Stellacci, Stefania Lo Cicero, Marialetizia Motta, Rosalba Carrozzo, Maria Lisa Dentici, Kirsty McWalter, Megha Desai, Kristin G Monaghan Show all



Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disord..

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Awarded by Italian Ministry of Health

Awarded by Institute for Maternal and Child Health IRCCS Burlo Garofolo

Awarded by Netherlands Organisation for Scientific Research (ZonMW Veni)

Awarded by NIH

Awarded by National Heart, Lung, and Blood Institute

Awarded by National Human Genome Research Institute

Awarded by Simons Foundation (SFARI)

Awarded by Health Innovation Challenge Fund

Funding Acknowledgements

The authors thank the participating families and Claudia Nardini (Ospedale Pediatrico Bambino Gesu, Rome) and Serenella Venanzi (Istituto Superiore di Sanita, Rome) for technical assistance. This workwas supported, inpart, by Fondazione BambinoGesu` (Vite Coraggiose toM.T.), Italian Ministry of Health(CCR-2017-23669081 and RCR-2020-23670068_001 to M.T.; RF-2018-12366931 to F.C.R. and B.D.; RC11/16-Institute for Maternal and Child Health IRCCS Burlo Garofolo and RCR-2019-23669117_001 to F.F., L.M., and P.G.), Netherlands Organisation for Scientific Research (ZonMW Veni) (grant 91617021 to T.S.B.), Brain & Behavior Research Foundation (NARSAD Young Investigator Grant to T.S.B.), NIH (R01HD098458 to D.A.S.), andGenome Canada (Genomic Applications Partnership Program grant to B.S.). Sequencing and data analysis of subject 14 were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute, National Eye Institute, and National Heart, Lung, and Blood Institute (UM1 HG008900) and by the National Human Genome Research Institute (R01 HG009141). Sequencing and data analyses of subjects 33 and 34 were supported bytheNIH(R01MH101221toE.E.E.) andSimons Foundation (SFARI #608045 to E.E.E.). The Deciphering Developmental Disorders (DDD) study presents independent research commissioned by the Health Innovation Challenge Fund (grant HICF-1009-003). This study makes use of DECIPHER, which is funded by the Wellcome. This work has been carried out in the frame of the ERN-ITHACA research activities.