Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

Lauren O'Grady; Samantha A. Schrier Vergano; Trevor L. Hoffman; Dean Sarco; Sara Cherny; Emily Bryant; Laura Schultz-Rogers; Wendy K. Chung; Stephanie Sacharow; Ladonna L. Immken; Susan Holder; Rebecca R. Blackwell; Catherine Buchanan; Roman Yusupov; François Lecoquierre; Anne Marie Guerrot; Lance Rodan; Bert B.A. de Vries; Erik Jan Kamsteeg; Fernando Santos Simarro; Maria Palomares-Bralo; Natasha Brown; Lynn Pais; Alejandro Ferrer; Eric W. Klee; Dusica Babovic-Vuksanovic; Lindsay Rhodes; Richard Person; Amber Begtrup; Jennifer Keller-Ramey; Teresa Santiago-Sim; Rhonda E. Schnur; David A. Sweetser; Nina B. Gold

doi:10.1002/ajmg.a.62772

Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

Lauren O'Grady, Samantha A. Schrier Vergano, Trevor L. Hoffman, Dean Sarco, Sara Cherny, Emily Bryant, Laura Schultz-Rogers, Wendy K. Chung, Stephanie Sacharow, Ladonna L. Immken, Susan Holder, Rebecca R. Blackwell, Catherine Buchanan, Roman Yusupov, François Lecoquierre, Anne Marie Guerrot, Lance Rodan, Bert B.A. de Vries, Erik Jan Kamsteeg, Fernando Santos SimarroMaria Palomares-Bralo, Natasha Brown, Lynn Pais, Alejandro Ferrer, Eric W. Klee, Dusica Babovic-Vuksanovic, Lindsay Rhodes, Richard Person, Amber Begtrup, Jennifer Keller-Ramey, Teresa Santiago-Sim, Rhonda E. Schnur, David A. Sweetser, Nina B. Gold

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	2750-2759
Number of pages	10
Journal	American Journal of Medical Genetics, Part A
Volume	188
Issue number	9
DOIs	https://doi.org/10.1002/ajmg.a.62772
State	Published - Sep 2022

Keywords

autism
exome sequencing
neurodevelopmental disabilities
retinitis pigmentosa

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1002/ajmg.a.62772

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O'Grady, L., Schrier Vergano, S. A., Hoffman, T. L., Sarco, D., Cherny, S., Bryant, E., Schultz-Rogers, L., Chung, W. K., Sacharow, S., Immken, L. L., Holder, S., Blackwell, R. R., Buchanan, C., Yusupov, R., Lecoquierre, F., Guerrot, A. M., Rodan, L., de Vries, B. B. A., Kamsteeg, E. J., ... Gold, N. B. (2022). Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders. American Journal of Medical Genetics, Part A, 188(9), 2750-2759. https://doi.org/10.1002/ajmg.a.62772

O'Grady, L, Schrier Vergano, SA, Hoffman, TL, Sarco, D, Cherny, S, Bryant, E, Schultz-Rogers, L, Chung, WK, Sacharow, S, Immken, LL, Holder, S, Blackwell, RR, Buchanan, C, Yusupov, R, Lecoquierre, F, Guerrot, AM, Rodan, L, de Vries, BBA, Kamsteeg, EJ, Santos Simarro, F, Palomares-Bralo, M, Brown, N, Pais, L, Ferrer, A , Klee, EW , Babovic-Vuksanovic, D, Rhodes, L, Person, R, Begtrup, A, Keller-Ramey, J, Santiago-Sim, T, Schnur, RE, Sweetser, DA & Gold, NB 2022, 'Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders', American Journal of Medical Genetics, Part A, vol. 188, no. 9, pp. 2750-2759. https://doi.org/10.1002/ajmg.a.62772

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title = "Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders",

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",

author = "Lauren O'Grady and {Schrier Vergano}, {Samantha A.} and Hoffman, {Trevor L.} and Dean Sarco and Sara Cherny and Emily Bryant and Laura Schultz-Rogers and Chung, {Wendy K.} and Stephanie Sacharow and Immken, {Ladonna L.} and Susan Holder and Blackwell, {Rebecca R.} and Catherine Buchanan and Roman Yusupov and Fran{\c c}ois Lecoquierre and Guerrot, {Anne Marie} and Lance Rodan and {de Vries}, {Bert B.A.} and Kamsteeg, {Erik Jan} and {Santos Simarro}, Fernando and Maria Palomares-Bralo and Natasha Brown and Lynn Pais and Alejandro Ferrer and Klee, {Eric W.} and Dusica Babovic-Vuksanovic and Lindsay Rhodes and Richard Person and Amber Begtrup and Jennifer Keller-Ramey and Teresa Santiago-Sim and Schnur, {Rhonda E.} and Sweetser, {David A.} and Gold, {Nina B.}",

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doi = "10.1002/ajmg.a.62772",

language = "English (US)",

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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.

PY - 2022/9

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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.

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Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders

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Keywords

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