ARF1 -related disorder: Phenotypic and molecular spectrum

Jean Madeleine De Sainte Agathe; Ben Pode-Shakked; Sophie Naudion; Vincent Michaud; Benoit Arveiler; Patricia Fergelot; Jean Delmas; Boris Keren; Céline Poirsier; Fowzan S. Alkuraya; Brahim Tabarki; Eric Bend; Kellie Davis; Martina Bebin; Michelle L. Thompson; Emily M. Bryant; Matias Wagner; Iris Hannibal; Jerica Lenberg; Martin Krenn; Kristen M. Wigby; Jennifer R. Friedman; Maria Iascone; Anna Cereda; Térence Miao; Eric Leguern; Emanuela Argilli; Elliott Sherr; Oana Caluseriu; Timothy Tidwell; Pinar Bayrak-Toydemir; Caroline Hagedorn; Melanie Brugger; Katharina Vill; Francois Dominique Morneau-Jacob; Wendy Chung; Kathryn N. Weaver; Joshua W. Owens; Ammar Husami; Bimal P. Chaudhari; Brandon S. Stone; Katie Burns; Rachel Li; Iris M. De Lange; Margaux Biehler; Emmanuelle Ginglinger; Bénédicte Gérard; Rolf W. Stottmann; Aurélien Trimouille

doi:10.1136/jmg-2022-108803

ARF1 -related disorder: Phenotypic and molecular spectrum

Jean Madeleine De Sainte Agathe^*, Ben Pode-Shakked, Sophie Naudion, Vincent Michaud, Benoit Arveiler, Patricia Fergelot, Jean Delmas, Boris Keren, Céline Poirsier, Fowzan S. Alkuraya, Brahim Tabarki, Eric Bend, Kellie Davis, Martina Bebin, Michelle L. Thompson, Emily M. Bryant, Matias Wagner, Iris Hannibal, Jerica Lenberg, Martin KrennKristen M. Wigby, Jennifer R. Friedman, Maria Iascone, Anna Cereda, Térence Miao, Eric Leguern, Emanuela Argilli, Elliott Sherr, Oana Caluseriu, Timothy Tidwell, Pinar Bayrak-Toydemir, Caroline Hagedorn, Melanie Brugger, Katharina Vill, Francois Dominique Morneau-Jacob, Wendy Chung, Kathryn N. Weaver, Joshua W. Owens, Ammar Husami, Bimal P. Chaudhari, Brandon S. Stone, Katie Burns, Rachel Li, Iris M. De Lange, Margaux Biehler, Emmanuelle Ginglinger, Bénédicte Gérard, Rolf W. Stottmann, Aurélien Trimouille

^*Corresponding author for this work

Pediatrics

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

4 Scopus citations

Abstract

Purpose ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. Methods We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. Results De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. Conclusion We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.

Original language	English
Pages (from-to)	999-1005
Number of pages	7
Journal	Journal of Medical Genetics
Volume	60
Issue number	10
DOIs	https://doi.org/10.1136/jmg-2022-108803
State	Published - 1 Oct 2023

Keywords

epilepsy
human genetics
sequence analysis, DNA

Access to Document

10.1136/jmg-2022-108803

Cite this

De Sainte Agathe, J. M., Pode-Shakked, B., Naudion, S., Michaud, V., Arveiler, B., Fergelot, P., Delmas, J., Keren, B., Poirsier, C., Alkuraya, F. S., Tabarki, B., Bend, E., Davis, K., Bebin, M., Thompson, M. L., Bryant, E. M., Wagner, M., Hannibal, I., Lenberg, J., ... Trimouille, A. (2023). ARF1 -related disorder: Phenotypic and molecular spectrum. Journal of Medical Genetics, 60(10), 999-1005. https://doi.org/10.1136/jmg-2022-108803

@article{b3eff276abe54e4c9e30d8b54bdf31b7,

title = "ARF1 -related disorder: Phenotypic and molecular spectrum",

abstract = "Purpose ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. Methods We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. Results De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. Conclusion We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.",

keywords = "epilepsy, human genetics, sequence analysis, DNA",

author = "{De Sainte Agathe}, {Jean Madeleine} and Ben Pode-Shakked and Sophie Naudion and Vincent Michaud and Benoit Arveiler and Patricia Fergelot and Jean Delmas and Boris Keren and C{\'e}line Poirsier and Alkuraya, {Fowzan S.} and Brahim Tabarki and Eric Bend and Kellie Davis and Martina Bebin and Thompson, {Michelle L.} and Bryant, {Emily M.} and Matias Wagner and Iris Hannibal and Jerica Lenberg and Martin Krenn and Wigby, {Kristen M.} and Friedman, {Jennifer R.} and Maria Iascone and Anna Cereda and T{\'e}rence Miao and Eric Leguern and Emanuela Argilli and Elliott Sherr and Oana Caluseriu and Timothy Tidwell and Pinar Bayrak-Toydemir and Caroline Hagedorn and Melanie Brugger and Katharina Vill and Morneau-Jacob, {Francois Dominique} and Wendy Chung and Weaver, {Kathryn N.} and Owens, {Joshua W.} and Ammar Husami and Chaudhari, {Bimal P.} and Stone, {Brandon S.} and Katie Burns and Rachel Li and {De Lange}, {Iris M.} and Margaux Biehler and Emmanuelle Ginglinger and B{\'e}n{\'e}dicte G{\'e}rard and Stottmann, {Rolf W.} and Aur{\'e}lien Trimouille",

year = "2023",

month = oct,

day = "1",

doi = "10.1136/jmg-2022-108803",

language = "אנגלית",

volume = "60",

pages = "999--1005",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

publisher = "BMJ Publishing Group",

number = "10",

}

De Sainte Agathe, JM, Pode-Shakked, B, Naudion, S, Michaud, V, Arveiler, B, Fergelot, P, Delmas, J, Keren, B, Poirsier, C, Alkuraya, FS, Tabarki, B, Bend, E, Davis, K, Bebin, M, Thompson, ML, Bryant, EM, Wagner, M, Hannibal, I, Lenberg, J, Krenn, M, Wigby, KM, Friedman, JR, Iascone, M, Cereda, A, Miao, T, Leguern, E, Argilli, E, Sherr, E, Caluseriu, O, Tidwell, T, Bayrak-Toydemir, P, Hagedorn, C, Brugger, M, Vill, K, Morneau-Jacob, FD, Chung, W, Weaver, KN, Owens, JW, Husami, A, Chaudhari, BP, Stone, BS, Burns, K, Li, R, De Lange, IM, Biehler, M, Ginglinger, E, Gérard, B, Stottmann, RW & Trimouille, A 2023, 'ARF1 -related disorder: Phenotypic and molecular spectrum', Journal of Medical Genetics, vol. 60, no. 10, pp. 999-1005. https://doi.org/10.1136/jmg-2022-108803

TY - JOUR

T1 - ARF1 -related disorder

T2 - Phenotypic and molecular spectrum

AU - De Sainte Agathe, Jean Madeleine

AU - Pode-Shakked, Ben

AU - Naudion, Sophie

AU - Michaud, Vincent

AU - Arveiler, Benoit

AU - Fergelot, Patricia

AU - Delmas, Jean

AU - Keren, Boris

AU - Poirsier, Céline

AU - Alkuraya, Fowzan S.

AU - Tabarki, Brahim

AU - Bend, Eric

AU - Davis, Kellie

AU - Bebin, Martina

AU - Thompson, Michelle L.

AU - Bryant, Emily M.

AU - Wagner, Matias

AU - Hannibal, Iris

AU - Lenberg, Jerica

AU - Krenn, Martin

AU - Wigby, Kristen M.

AU - Friedman, Jennifer R.

AU - Iascone, Maria

AU - Cereda, Anna

AU - Miao, Térence

AU - Leguern, Eric

AU - Argilli, Emanuela

AU - Sherr, Elliott

AU - Caluseriu, Oana

AU - Tidwell, Timothy

AU - Bayrak-Toydemir, Pinar

AU - Hagedorn, Caroline

AU - Brugger, Melanie

AU - Vill, Katharina

AU - Morneau-Jacob, Francois Dominique

AU - Chung, Wendy

AU - Weaver, Kathryn N.

AU - Owens, Joshua W.

AU - Husami, Ammar

AU - Chaudhari, Bimal P.

AU - Stone, Brandon S.

AU - Burns, Katie

AU - Li, Rachel

AU - De Lange, Iris M.

AU - Biehler, Margaux

AU - Ginglinger, Emmanuelle

AU - Gérard, Bénédicte

AU - Stottmann, Rolf W.

AU - Trimouille, Aurélien

PY - 2023/10/1

Y1 - 2023/10/1

N2 - Purpose ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. Methods We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. Results De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. Conclusion We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.

AB - Purpose ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. Methods We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. Results De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. Conclusion We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.

KW - epilepsy

KW - human genetics

KW - sequence analysis, DNA

UR - http://www.scopus.com/inward/record.url?scp=85159163004&partnerID=8YFLogxK

U2 - 10.1136/jmg-2022-108803

DO - 10.1136/jmg-2022-108803

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 37185208

AN - SCOPUS:85159163004

SN - 0022-2593

VL - 60

SP - 999

EP - 1005

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 10

ER -

ARF1 -related disorder: Phenotypic and molecular spectrum

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this