Publication: COL4A1-related autosomal recessive encephalopathy in 2 Turkish children
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Program
KU-Authors
KU Authors
Co-Authors
Yaramış, Ahmet
Lochmueller, Hanns
Topf, Ana
Sönmezler, Ece
Yılmaz, Elmasnur
Hız, Semra
Yiş, Uluç
Güngör, Serdal
Polat, Ayşe İpek
Edem, Pınar
Advisor
Publication Date
2020
Language
English
Type
Journal Article
Journal Title
Journal ISSN
Volume Title
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.
Description
Source:
Neurology: Genetics
Publisher:
Lippincott Williams and Wilkins (LWW)
Keywords:
Subject
Medicine, Malformations of cortical development, Mutation, Basement membranes