COL4A1-related autosomal recessive encephalopathy in 2 Turkish children

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

COL4A1-related autosomal recessive encephalopathy in 2 Turkish children

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dc.contributor.author Yaramis, Ahmet
dc.contributor.author Lochmüller, Hanns
dc.contributor.author Töpf, Ana
dc.contributor.author Sonmezler, Ece
dc.contributor.author Yilmaz, Elmasnur
dc.contributor.author Hiz, Semra
dc.contributor.author Yis, Uluc
dc.contributor.author Gungor, Serdal
dc.contributor.author Polat, Ayse Ipek
dc.contributor.author Edem, Pinar
dc.contributor.author Beltran, Sergi
dc.contributor.author Laurie, Steven, 1973-
dc.contributor.author Yaramis, Aysenur
dc.contributor.author Horvath, Rita
dc.contributor.author Oktay, Yavuz
dc.date.accessioned 2020-05-06T09:31:02Z
dc.date.available 2020-05-06T09:31:02Z
dc.date.issued 2020
dc.description.abstract 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.
dc.description.sponsorship 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)
dc.format.mimetype application/pdf
dc.identifier.citation Yaramis A, Lochmüller H, Töpf A, Sonmezler E, Yilmaz E, Hiz S et al. COL4A1-related autosomal recessive encephalopathy in 2 Turkish children. Neurol Genet. 2020 Jan 10; 6(1):e 392. DOI: 10.1212/NXG.0000000000000392
dc.identifier.doi http://dx.doi.org/10.1212/NXG.0000000000000392
dc.identifier.issn 2376-7839
dc.identifier.uri http://hdl.handle.net/10230/44436
dc.language.iso eng
dc.publisher Lippincott Williams & Wilkins
dc.relation.ispartof Neurology Genetics. 2020 Jan 10; 6(1):e 392
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309548
dc.rights © 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 cited
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Neurogenètica
dc.subject.other Encefalopatia
dc.subject.other Infants -- Malalties
dc.title COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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