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COL4A1 -related autosomal recessive encephalopathy in 2 Turkish children

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.

Publication metadata

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

Year: 2020

Volume: 6

Issue: 1

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


DOI: 10.1212/NXG.0000000000000392


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Funder referenceFunder name
201064/Z/16/ZWellcome Trust
109915/Z/15/ZWellcome Trust
203105/Z/16/ZWellcome Trust
MR/N025431/1Medical Research Council (MRC)
MR/N027302/1Medical Research Council (MRC)