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Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities
Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities
Purpose
Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.

Methods
We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature.

Results
The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss.

Conclusion
This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.
Chromatinopathy, Mendelian disorders of the epigenetic machinery, PRMT7, Syndromic neurodevelopmental disorder, Syndromic obesity
1098-3600
135-142
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Cali, Elisa, Suri, Mohnish, Scala, Marcello, Ferla, Matteo P, Alavi, Shadryar, Ali Faqeih, Eissa, Bijlsma, Emilia K, Wigby, Kristen M, Baralle, Diana, Mehrjardi, Mohammad Yahya Vahidi, Schwab, Jennifer, Platzer, Konrad, Steindl, Katharina, Hashem, Mais, Jones, Marilyn, Niyazov, Dmitriy M, Jacober, Jennifer, Littlejohn, Rebecca O., Weis, Denisa, Zadeh, Neda, Rodan, Lance, Goldenberg, Alice, Lecoquierre, Francois, Dutra-Clarke, Marina, Horvarth, Gabriella, Young, Dana, Orenstein, Naama, Bawazeer, Shahad, Vulto-van Silfhout, A.T., Herenger, Yvan, Dehghanian, M., Seyedhassani, Seyed Mohammad, Bahreini, Amir, Nasab, Mahya Ebrahimi, Ercan-Sencicek, A Gulhan, Firoozfar, Zahra, Movahedinia, Mojtaba, Efthymiou, Stephanie, Striano, Pasquale, Karimiani, Ehsan Ghayoor, Salpietro, Vincenzo, Taylor, Jenny C., Redman, Melody, Stegmann, Alexander P.A., Laner, Andrea, Abdel-Salam, Ghada, Li, Megan, Bengala, Mario, Muller, Amelie Johanna, Digilio, Maria Cristina, Rauch, Anita, Gunel, Murat, Titheradge, Hannah, Schweitzer, Daniela N, Kraus, Alison, Valenzuela, Irene, Mclean, Scott D, Phornphutkul, Chanika, Salih, Mustafa, Begtrup, Amber, Schnur, Rhonda E, Torti, Erin, Haack, Tobias B, Prada, Carlos E, Alkuraya, Fowzan S, Houlden, Henry and Maroofian, Reza (2023) Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities. Genetics in Medicine, 25 (1), 135-142. (doi:10.1016/j.gim.2022.09.016).

Record type: Article

Abstract

Purpose
Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.

Methods
We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature.

Results
The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss.

Conclusion
This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.

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Accepted/In Press date: 28 September 2022
e-pub ahead of print date: 18 November 2022
Published date: 1 January 2023
Keywords: Chromatinopathy, Mendelian disorders of the epigenetic machinery, PRMT7, Syndromic neurodevelopmental disorder, Syndromic obesity

Identifiers

Local EPrints ID: 472172
URI: http://eprints.soton.ac.uk/id/eprint/472172
ISSN: 1098-3600
PURE UUID: dc238c36-9b23-45c8-a67d-9497fc526d74
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 28 Nov 2022 18:09
Last modified: 14 Jan 2023 02:42

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Contributors

Author: Elisa Cali
Author: Mohnish Suri
Author: Marcello Scala
Author: Matteo P Ferla
Author: Shadryar Alavi
Author: Eissa Ali Faqeih
Author: Emilia K Bijlsma
Author: Kristen M Wigby
Author: Diana Baralle ORCID iD
Author: Mohammad Yahya Vahidi Mehrjardi
Author: Jennifer Schwab
Author: Konrad Platzer
Author: Katharina Steindl
Author: Mais Hashem
Author: Marilyn Jones
Author: Dmitriy M Niyazov
Author: Jennifer Jacober
Author: Rebecca O. Littlejohn
Author: Denisa Weis
Author: Neda Zadeh
Author: Lance Rodan
Author: Alice Goldenberg
Author: Francois Lecoquierre
Author: Marina Dutra-Clarke
Author: Gabriella Horvarth
Author: Dana Young
Author: Naama Orenstein
Author: Shahad Bawazeer
Author: A.T. Vulto-van Silfhout
Author: Yvan Herenger
Author: M. Dehghanian
Author: Seyed Mohammad Seyedhassani
Author: Amir Bahreini
Author: Mahya Ebrahimi Nasab
Author: A Gulhan Ercan-Sencicek
Author: Zahra Firoozfar
Author: Mojtaba Movahedinia
Author: Stephanie Efthymiou
Author: Pasquale Striano
Author: Ehsan Ghayoor Karimiani
Author: Vincenzo Salpietro
Author: Jenny C. Taylor
Author: Melody Redman
Author: Alexander P.A. Stegmann
Author: Andrea Laner
Author: Ghada Abdel-Salam
Author: Megan Li
Author: Mario Bengala
Author: Amelie Johanna Muller
Author: Maria Cristina Digilio
Author: Anita Rauch
Author: Murat Gunel
Author: Hannah Titheradge
Author: Daniela N Schweitzer
Author: Alison Kraus
Author: Irene Valenzuela
Author: Scott D Mclean
Author: Chanika Phornphutkul
Author: Mustafa Salih
Author: Amber Begtrup
Author: Rhonda E Schnur
Author: Erin Torti
Author: Tobias B Haack
Author: Carlos E Prada
Author: Fowzan S Alkuraya
Author: Henry Houlden
Author: Reza Maroofian

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