Case Reports

. 2022 Sep;188(9):2750-2759.

doi: 10.1002/ajmg.a.62772. Epub 2022 May 11.

Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

Lauren O'Grady^{1

2}, Samantha A Schrier Vergano^{3

4}, Trevor L Hoffman⁵, Dean Sarco⁶, Sara Cherny⁷, Emily Bryant⁸, Laura Schultz-Rogers⁹, Wendy K Chung¹⁰, Stephanie Sacharow^{11

12}, Ladonna L Immken¹³, Susan Holder¹³, Rebecca R Blackwell¹³, Catherine Buchanan¹³, Roman Yusupov¹⁴, François Lecoquierre¹⁵, Anne-Marie Guerrot¹⁵, Lance Rodan^{11

12}, Bert B A de Vries¹⁶, Erik Jan Kamsteeg¹⁶, Fernando Santos Simarro¹⁷, Maria Palomares-Bralo¹⁷, Natasha Brown^{18

19}, Lynn Pais²⁰, Alejandro Ferrer²¹, Eric W Klee²¹, Dusica Babovic-Vuksanovic²¹, Lindsay Rhodes²², Richard Person²², Amber Begtrup²², Jennifer Keller-Ramey²², Teresa Santiago-Sim²², Rhonda E Schnur²², David A Sweetser¹, Nina B Gold¹

Affiliations

¹ Division of Medical Genetics and Metabolism, Massachusetts General Hospital for Children, Boston, Massachusetts, USA.
² MGH Institute of Health Professions, Charlestown, Massachusetts, USA.
³ Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughter, Norfolk, Virginia, USA.
⁴ Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, USA.
⁵ Department of Genetics, Southern California Kaiser Permanente Medical Group, Anaheim, California, USA.
⁶ Department of Neurology, Kaiser Permanente-Los Angeles Medical Center, Los Angeles, California, USA.
⁷ Division of Cardiology, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.
⁸ Division of Neurology, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.
⁹ Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁰ Department of Pediatrics and Medicine, Columbia University Irving Medical Center, New York, New York, USA.
¹¹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
¹² Harvard Medical School, Boston, Massachusetts, USA.
¹³ Department of Clinical & Metabolic Genetics, Dell Children's Medical Group, Austin, Texas, USA.
¹⁴ Division of Pediatric Genetics, Joe DiMaggio Children's Hospital, Hollywood, Florida, USA.
¹⁵ Department of Genetics and Reference Center for Developmental Disorders, FHU G4 Génomique, Normandie University, UNIROUEN, Inserm U1245, CHU Rouen, Rouen, France.
¹⁶ Department of Human Genetics, Radboud University Medical Center and Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
¹⁷ Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.
¹⁸ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
¹⁹ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
²⁰ Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
²¹ Center for Individualized Medicine, Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
²² GeneDx, Inc., Gaithersburg, Maryland, USA.

PMID: 35543142
DOI: 10.1002/ajmg.a.62772

Case Reports

Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

Lauren O'Grady et al. Am J Med Genet A. 2022 Sep.

. 2022 Sep;188(9):2750-2759.

doi: 10.1002/ajmg.a.62772. Epub 2022 May 11.

Authors

Affiliations

¹ Division of Medical Genetics and Metabolism, Massachusetts General Hospital for Children, Boston, Massachusetts, USA.
² MGH Institute of Health Professions, Charlestown, Massachusetts, USA.
³ Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughter, Norfolk, Virginia, USA.
⁴ Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, USA.
⁵ Department of Genetics, Southern California Kaiser Permanente Medical Group, Anaheim, California, USA.
⁶ Department of Neurology, Kaiser Permanente-Los Angeles Medical Center, Los Angeles, California, USA.
⁷ Division of Cardiology, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.
⁸ Division of Neurology, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.
⁹ Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁰ Department of Pediatrics and Medicine, Columbia University Irving Medical Center, New York, New York, USA.
¹¹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
¹² Harvard Medical School, Boston, Massachusetts, USA.
¹³ Department of Clinical & Metabolic Genetics, Dell Children's Medical Group, Austin, Texas, USA.
¹⁴ Division of Pediatric Genetics, Joe DiMaggio Children's Hospital, Hollywood, Florida, USA.
¹⁵ Department of Genetics and Reference Center for Developmental Disorders, FHU G4 Génomique, Normandie University, UNIROUEN, Inserm U1245, CHU Rouen, Rouen, France.
¹⁶ Department of Human Genetics, Radboud University Medical Center and Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
¹⁷ Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.
¹⁸ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
¹⁹ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
²⁰ Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
²¹ Center for Individualized Medicine, Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
²² GeneDx, Inc., Gaithersburg, Maryland, USA.

PMID: 35543142
DOI: 10.1002/ajmg.a.62772

Abstract

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.

Keywords: autism; exome sequencing; neurodevelopmental disabilities; retinitis pigmentosa.

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Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

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Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

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