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

Elisa Cali; Mohnish Suri; Marcello Scala; Matteo P Ferla; Shahryar Alavi; Eissa Ali Faqeih; Emilia K Bijlsma; Kristen M Wigby; Diana Baralle; Mohammad Y V Mehrjardi; Jennifer Schwab; Konrad Platzer; Katharina Steindl; Mais Hashem; Marilyn Jones; Dmitriy M Niyazov; Jennifer Jacober; Rebecca Okashah Littlejohn; Denisa Weis; Neda Zadeh; Lance Rodan; Alice Goldenberg; François Lecoquierre; Marina Dutra-Clarke; Gabriella Horvath; Dana Young; Naama Orenstein; Shahad Bawazeer; Anneke T Vulto-van Silfhout; Yvan Herenger; Mohammadreza Dehghani; Seyed Mohammad Seyedhassani; Amir Bahreini; Mahya E Nasab; A Gulhan Ercan-Sencicek; Zahra Firoozfar; Mojtaba Movahedinia; Stephanie Efthymiou; Pasquale Striano; Ehsan Ghayoor Karimiani; Vincenzo Salpietro; Jenny C Taylor; Melody Redman; Alexander P A Stegmann; Andreas Laner; Ghada Abdel-Salam; Megan Li; Mario Bengala; Amelie Johanna Müller; Maria C Digilio; Reza Maroofian; Author collaboration

doi:10.1016/j.gim.2022.09.016

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

Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K Bijlsma, Kristen M Wigby, Diana Baralle, Mohammad Y V Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda ZadehLance Rodan, Alice Goldenberg, François Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T Vulto-van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E Nasab, A Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C Taylor, Melody Redman, Alexander P A Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Müller, Maria C Digilio, Reza Maroofian^*, Author collaboration

^*Corresponding author for this work

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

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.

Original language	English
Pages (from-to)	135-142
Number of pages	8
Journal	Genetics in Medicine
Volume	25
Issue number	1
Early online date	17 Nov 2022
DOIs	https://doi.org/10.1016/j.gim.2022.09.016
Publication status	Published - Jan 2023

Access to Document

10.1016/j.gim.2022.09.016Licence: CC BY

Cite this

Cali, E., Suri, M., Scala, M., Ferla, M. P., Alavi, S., Faqeih, E. A., Bijlsma, E. K., Wigby, K. M., Baralle, D., Mehrjardi, M. Y. V., Schwab, J., Platzer, K., Steindl, K., Hashem, M., Jones, M., Niyazov, D. M., Jacober, J., Littlejohn, R. O., Weis, D., ... Author collaboration (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. https://doi.org/10.1016/j.gim.2022.09.016

@article{81d27084ec1f4ef6a38c5c73866a5a8e,

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

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.",

author = "Elisa Cali and Mohnish Suri and Marcello Scala and Ferla, {Matteo P} and Shahryar Alavi and Faqeih, {Eissa Ali} and Bijlsma, {Emilia K} and Wigby, {Kristen M} and Diana Baralle and Mehrjardi, {Mohammad Y V} and Jennifer Schwab and Konrad Platzer and Katharina Steindl and Mais Hashem and Marilyn Jones and Niyazov, {Dmitriy M} and Jennifer Jacober and Littlejohn, {Rebecca Okashah} and Denisa Weis and Neda Zadeh and Lance Rodan and Alice Goldenberg and Fran{\c c}ois Lecoquierre and Marina Dutra-Clarke and Gabriella Horvath and Dana Young and Naama Orenstein and Shahad Bawazeer and {Vulto-van Silfhout}, {Anneke T} and Yvan Herenger and Mohammadreza Dehghani and Seyedhassani, {Seyed Mohammad} and Amir Bahreini and Nasab, {Mahya E} and Ercan-Sencicek, {A Gulhan} and Zahra Firoozfar and Mojtaba Movahedinia and Stephanie Efthymiou and Pasquale Striano and Karimiani, {Ehsan Ghayoor} and Vincenzo Salpietro and Taylor, {Jenny C} and Melody Redman and Stegmann, {Alexander P A} and Andreas Laner and Ghada Abdel-Salam and Megan Li and Mario Bengala and M{\"u}ller, {Amelie Johanna} and Digilio, {Maria C} and Reza Maroofian and {Author collaboration}",

year = "2023",

month = jan,

doi = "10.1016/j.gim.2022.09.016",

language = "English",

volume = "25",

pages = "135--142",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Nature Publishing Group",

number = "1",

}

Cali, E, Suri, M, Scala, M, Ferla, MP, Alavi, S, Faqeih, EA, Bijlsma, EK, Wigby, KM, Baralle, D, Mehrjardi, MYV, Schwab, J, Platzer, K, Steindl, K, Hashem, M, Jones, M, Niyazov, DM, Jacober, J, Littlejohn, RO, Weis, D, Zadeh, N, Rodan, L, Goldenberg, A, Lecoquierre, F, Dutra-Clarke, M, Horvath, G, Young, D, Orenstein, N, Bawazeer, S, Vulto-van Silfhout, AT, Herenger, Y, Dehghani, M, Seyedhassani, SM, Bahreini, A, Nasab, ME, Ercan-Sencicek, AG, Firoozfar, Z, Movahedinia, M, Efthymiou, S, Striano, P, Karimiani, EG, Salpietro, V, Taylor, JC, Redman, M, Stegmann, APA, Laner, A, Abdel-Salam, G, Li, M, Bengala, M, Müller, AJ, Digilio, MC, Maroofian, R & Author collaboration 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, vol. 25, no. 1, pp. 135-142. https://doi.org/10.1016/j.gim.2022.09.016

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities. / Cali, Elisa; Suri, Mohnish; Scala, Marcello et al.
In: Genetics in Medicine, Vol. 25, No. 1, 01.2023, p. 135-142.

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

TY - JOUR

T1 - Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities

AU - Cali, Elisa

AU - Suri, Mohnish

AU - Scala, Marcello

AU - Ferla, Matteo P

AU - Alavi, Shahryar

AU - Faqeih, Eissa Ali

AU - Bijlsma, Emilia K

AU - Wigby, Kristen M

AU - Baralle, Diana

AU - Mehrjardi, Mohammad Y V

AU - Schwab, Jennifer

AU - Platzer, Konrad

AU - Steindl, Katharina

AU - Hashem, Mais

AU - Jones, Marilyn

AU - Niyazov, Dmitriy M

AU - Jacober, Jennifer

AU - Littlejohn, Rebecca Okashah

AU - Weis, Denisa

AU - Zadeh, Neda

AU - Rodan, Lance

AU - Goldenberg, Alice

AU - Lecoquierre, François

AU - Dutra-Clarke, Marina

AU - Horvath, Gabriella

AU - Young, Dana

AU - Orenstein, Naama

AU - Bawazeer, Shahad

AU - Vulto-van Silfhout, Anneke T

AU - Herenger, Yvan

AU - Dehghani, Mohammadreza

AU - Seyedhassani, Seyed Mohammad

AU - Bahreini, Amir

AU - Nasab, Mahya E

AU - Ercan-Sencicek, A Gulhan

AU - Firoozfar, Zahra

AU - Movahedinia, Mojtaba

AU - Efthymiou, Stephanie

AU - Striano, Pasquale

AU - Karimiani, Ehsan Ghayoor

AU - Salpietro, Vincenzo

AU - Taylor, Jenny C

AU - Redman, Melody

AU - Stegmann, Alexander P A

AU - Laner, Andreas

AU - Abdel-Salam, Ghada

AU - Li, Megan

AU - Bengala, Mario

AU - Müller, Amelie Johanna

AU - Digilio, Maria C

AU - Maroofian, Reza

AU - Author collaboration

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.gim.2022.09.016

DO - 10.1016/j.gim.2022.09.016

M3 - Article

C2 - 36399134

SN - 1098-3600

VL - 25

SP - 135

EP - 142

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 1

ER -