TY - JOUR
T1 - Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders
AU - O'Grady, Lauren
AU - Schrier Vergano, Samantha A.
AU - Hoffman, Trevor L.
AU - Sarco, Dean
AU - Cherny, Sara
AU - Bryant, Emily
AU - Schultz-Rogers, Laura
AU - Chung, Wendy K.
AU - Sacharow, Stephanie
AU - Immken, Ladonna L.
AU - Holder, Susan
AU - Blackwell, Rebecca R.
AU - Buchanan, Catherine
AU - Yusupov, Roman
AU - Lecoquierre, François
AU - Guerrot, Anne Marie
AU - Rodan, Lance
AU - de Vries, Bert B.A.
AU - Kamsteeg, Erik Jan
AU - Santos Simarro, Fernando
AU - Palomares-Bralo, Maria
AU - Brown, Natasha
AU - Pais, Lynn
AU - Ferrer, Alejandro
AU - Klee, Eric W.
AU - Babovic-Vuksanovic, Dusica
AU - Rhodes, Lindsay
AU - Person, Richard
AU - Begtrup, Amber
AU - Keller-Ramey, Jennifer
AU - Santiago-Sim, Teresa
AU - Schnur, Rhonda E.
AU - Sweetser, David A.
AU - Gold, Nina B.
N1 - Funding Information:
This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org . Funding for the DECIPHER project was provided by Wellcome.
Funding Information:
The Genotype‐Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscriptwere obtained from: the GTEx Portal on 05/19/2021 and dbGAP Accession phs000424.v8.p2. This work was financially supported by grants from the Dutch Organization for Health Research and Development (ZON‐MW grants 917–86–319 and 912–12–109 to Bert B. A. de Vries).
Funding Information:
This work was in part supported by the Brooks S Hill Fund for Medical Genetics at MassGeneral Hospital for Children and a donation by Seta and Douglas Atamian.
Funding Information:
We would like to thank the patients and their families for their participation in this publication. This work was in part supported by the Brooks S Hill Fund for Medical Genetics at MassGeneral Hospital for Children and a donation by Seta and Douglas Atamian. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscriptwere obtained from: the GTEx Portal on 05/19/2021 and dbGAP Accession phs000424.v8.p2. This work was financially supported by grants from the Dutch Organization for Health Research and Development (ZON-MW grants 917–86–319 and 912–12–109 to Bert B. A. de Vries). This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org. Funding for the DECIPHER project was provided by Wellcome. Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. This study makes use of data shared through the PhenomeCentral repository. Funding for PhenomeCentral was provided by Genome Canada and Canadian Institute of Health Research (CIHR). Buske, O. J.*, Girdea, M.*, Dumitriu, S., Gallinger, B., Hartley, T., Trang, H., Misyura, A., Friedman, T., Beaulieu, C., Bone, W. P., Links, A. E., Washington, N. L., Haendel, M. A., Robinson, P. N., Boerkoel, C. F., Adams, D., Gahl, W. A., Boycott, K. M., Brudno, M. (2015). PhenomeCentral: A portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases. Human Mutation, 36, 931–940. doi:10.1002/humu.22851; https://www.phenomecentral.org/.
Funding Information:
This study makes use of data shared through the PhenomeCentral repository. Funding for PhenomeCentral was provided by Genome Canada and Canadian Institute of Health Research (CIHR). Buske, O. J.*, Girdea, M.*, Dumitriu, S., Gallinger, B., Hartley, T., Trang, H., Misyura, A., Friedman, T., Beaulieu, C., Bone, W. P., Links, A. E., Washington, N. L., Haendel, M. A., Robinson, P. N., Boerkoel, C. F., Adams, D., Gahl, W. A., Boycott, K. M., Brudno, M. (2015). PhenomeCentral: A portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases. , , 931–940. doi:10.1002/humu.22851; https://www.phenomecentral.org/. Human Mutation 36
Funding Information:
Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141.
Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/9
Y1 - 2022/9
N2 - The pre-mRNA-processing factor 8, encoded by PRPF8, is a scaffolding component of a spliceosome complex involved in the removal of introns from mRNA precursors. Previously, heterozygous pathogenic variants in PRPF8 have been associated with autosomal dominant retinitis pigmentosa. More recently, PRPF8 was suggested as a candidate gene for autism spectrum disorder due to the enrichment of sequence variants in this gene in individuals with neurodevelopmental disorders. We report 14 individuals with various forms of neurodevelopmental conditions, found to have heterozygous, predominantly de novo, missense, and loss-of-function variants in PRPF8. These individuals have clinical features that may represent a new neurodevelopmental syndrome.
AB - The pre-mRNA-processing factor 8, encoded by PRPF8, is a scaffolding component of a spliceosome complex involved in the removal of introns from mRNA precursors. Previously, heterozygous pathogenic variants in PRPF8 have been associated with autosomal dominant retinitis pigmentosa. More recently, PRPF8 was suggested as a candidate gene for autism spectrum disorder due to the enrichment of sequence variants in this gene in individuals with neurodevelopmental disorders. We report 14 individuals with various forms of neurodevelopmental conditions, found to have heterozygous, predominantly de novo, missense, and loss-of-function variants in PRPF8. These individuals have clinical features that may represent a new neurodevelopmental syndrome.
KW - autism
KW - exome sequencing
KW - neurodevelopmental disabilities
KW - retinitis pigmentosa
UR - http://www.scopus.com/inward/record.url?scp=85129729324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129729324&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.62772
DO - 10.1002/ajmg.a.62772
M3 - Article
C2 - 35543142
AN - SCOPUS:85129729324
SN - 1552-4825
VL - 188
SP - 2750
EP - 2759
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 9
ER -