COL4A1-related autosomal recessive encephalopathy in 2 Turkish children

OBJECTIVE: This study presents the neurologic phenotypes of 2 brothers with a novel homozygous COL4A1 mutation that was identified in a large Turkish consanguineous cohort of neurogenetic diseases. METHODS: Whole-exome sequencing and bioinformatic analysis of consanguineous families with children af...

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Authors: Yaramis, Ahmet, Lochmüller, Hanns, Töpf, Ana, Sonmezler, Ece, Yilmaz, Elmasnur, Hiz, Semra, Yis, Uluc, Gungor, Serdal, Polat, Ayse Ipek, Edem, Pinar, Beltran, Sergi, Laurie, Steven, 1973-, Yaramis, Aysenur, Horvath, Rita, Oktay, Yavuz
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44436
Online Access:http://hdl.handle.net/10230/44436
http://dx.doi.org/10.1212/NXG.0000000000000392
Access Level:Open access
Keyword:Neurogenètica
Encefalopatia
Infants -- Malalties
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spelling COL4A1-related autosomal recessive encephalopathy in 2 Turkish childrenYaramis, AhmetLochmüller, HannsTöpf, AnaSonmezler, EceYilmaz, ElmasnurHiz, SemraYis, UlucGungor, SerdalPolat, Ayse IpekEdem, PinarBeltran, SergiLaurie, Steven, 1973-Yaramis, AysenurHorvath, RitaOktay, YavuzNeurogenèticaEncefalopatiaInfants -- MalaltiesOBJECTIVE: This study presents the neurologic phenotypes of 2 brothers with a novel homozygous COL4A1 mutation that was identified in a large Turkish consanguineous cohort of neurogenetic diseases. METHODS: Whole-exome sequencing and bioinformatic analysis of consanguineous families with children affected by early-onset, neurogenetic disorders was performed using the RD-Connect Genome-Phenome Analysis Platform. We also performed clinical, EEG, and neuroimaging analyses in unaffected siblings and parents. RESULTS: We have identified a homozygous missense mutation in COL4A1 (p.Gly1278Ser, NM_001845.5:c.3832G>T) in 2 siblings affected by small vessel brain disease with periventricular leukoencephalopathy and ocular defects. Presenting symptoms included mild weakness, hemiparetic gait, pyramidal findings, and seizures, whereas their intellectual and behavioral functions were normal. Both parents and 5 of the siblings (3 boys and 2 girls) were heterozygous for the variant. They did not show any clinical or laboratory signs of small vessel disease. CONCLUSIONS: COL4A1 has previously been associated with dominant small vessel disease of the brain and other organs, manifesting with high penetrance in heterozygous mutation carriers. Our findings provide evidence that COL4A1-related encephalopathy can be inherited in an autosomal recessive manner, which is important for counseling, prognosis, and treatment. Genotype-phenotype correlations remain to be established.This study was supported by the Turkish Scientific and Research Council (TUBITAK) research grant 216S771 (A. Yaramis, S. Hiz, U. Yis, S. Gungor, and Y. Oktay). R. Horvath is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z), and the Newton Fund (UK/Turkey, MR/N027302/1)Lippincott Williams & Wilkins202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44436http://dx.doi.org/10.1212/NXG.0000000000000392reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNeurology Genetics. 2020 Jan 10; 6(1):e 392info:eu-repo/grantAgreement/EC/FP7/309548© 2020 by Ahmet Yaramis et al. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/444362026-06-12T07:21:37Z
dc.title.none.fl_str_mv COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
title COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
spellingShingle COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
Yaramis, Ahmet
Neurogenètica
Encefalopatia
Infants -- Malalties
title_short COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
title_full COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
title_fullStr COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
title_full_unstemmed COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
title_sort COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
dc.creator.none.fl_str_mv Yaramis, Ahmet
Lochmüller, Hanns
Töpf, Ana
Sonmezler, Ece
Yilmaz, Elmasnur
Hiz, Semra
Yis, Uluc
Gungor, Serdal
Polat, Ayse Ipek
Edem, Pinar
Beltran, Sergi
Laurie, Steven, 1973-
Yaramis, Aysenur
Horvath, Rita
Oktay, Yavuz
author Yaramis, Ahmet
author_facet Yaramis, Ahmet
Lochmüller, Hanns
Töpf, Ana
Sonmezler, Ece
Yilmaz, Elmasnur
Hiz, Semra
Yis, Uluc
Gungor, Serdal
Polat, Ayse Ipek
Edem, Pinar
Beltran, Sergi
Laurie, Steven, 1973-
Yaramis, Aysenur
Horvath, Rita
Oktay, Yavuz
author_role author
author2 Lochmüller, Hanns
Töpf, Ana
Sonmezler, Ece
Yilmaz, Elmasnur
Hiz, Semra
Yis, Uluc
Gungor, Serdal
Polat, Ayse Ipek
Edem, Pinar
Beltran, Sergi
Laurie, Steven, 1973-
Yaramis, Aysenur
Horvath, Rita
Oktay, Yavuz
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Neurogenètica
Encefalopatia
Infants -- Malalties
topic Neurogenètica
Encefalopatia
Infants -- Malalties
description OBJECTIVE: This study presents the neurologic phenotypes of 2 brothers with a novel homozygous COL4A1 mutation that was identified in a large Turkish consanguineous cohort of neurogenetic diseases. METHODS: Whole-exome sequencing and bioinformatic analysis of consanguineous families with children affected by early-onset, neurogenetic disorders was performed using the RD-Connect Genome-Phenome Analysis Platform. We also performed clinical, EEG, and neuroimaging analyses in unaffected siblings and parents. RESULTS: We have identified a homozygous missense mutation in COL4A1 (p.Gly1278Ser, NM_001845.5:c.3832G>T) in 2 siblings affected by small vessel brain disease with periventricular leukoencephalopathy and ocular defects. Presenting symptoms included mild weakness, hemiparetic gait, pyramidal findings, and seizures, whereas their intellectual and behavioral functions were normal. Both parents and 5 of the siblings (3 boys and 2 girls) were heterozygous for the variant. They did not show any clinical or laboratory signs of small vessel disease. CONCLUSIONS: COL4A1 has previously been associated with dominant small vessel disease of the brain and other organs, manifesting with high penetrance in heterozygous mutation carriers. Our findings provide evidence that COL4A1-related encephalopathy can be inherited in an autosomal recessive manner, which is important for counseling, prognosis, and treatment. Genotype-phenotype correlations remain to be established.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44436
http://dx.doi.org/10.1212/NXG.0000000000000392
url http://hdl.handle.net/10230/44436
http://dx.doi.org/10.1212/NXG.0000000000000392
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Neurology Genetics. 2020 Jan 10; 6(1):e 392
info:eu-repo/grantAgreement/EC/FP7/309548
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams & Wilkins
publisher.none.fl_str_mv Lippincott Williams & Wilkins
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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