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Lookup NU author(s): Professor Hanns Lochmuller,
Dr Ana TopfORCiD,
Professor Rita HorvathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© American Academy of Neurology.ObjectiveThis 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.MethodsWhole-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.ResultsWe 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.ConclusionsCOL4A1 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.
Author(s): Yaramis A, Lochmuller H, Topf A, Sonmezler E, Yilmaz E, Hiz S, Yis U, Gungor S, Polat AI, Edem P, Beltran S, Laurie S, Yaramis A, Horvath R, Oktay Y
Publication type: Article
Publication status: Published
Journal: Neurology: Genetics
Online publication date: 10/01/2020
Acceptance date: 08/10/2019
Date deposited: 31/03/2020
ISSN (electronic): 2376-7839
Publisher: Lippincott Williams and Wilkins
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