New Publication: COL4A1-related autosomal recessive encephalopathy in 2 Turkish children

We are happy to have been involved with this paper presenting the neurological phenotypes of 2 Turkish brothers with a novel mutation. Through whole-exome sequencing and analysis using the RD-Connect Genome-Phenome Analysis Platform, we helped to identify a rare case of autosomal recessive inheritance of homozygous missense COL4A1 variants. Widening the clinical spectrum and defining an unusual inheritance pattern of these variants will help clinicians target screening for COL4A1, thus allowing for more appropriate clinical care.

You can read the article on Neurology genetics here.

COL4A1-related autosomal recessive encephalopathy in 2 Turkish children

Ahmet YaramisHanns LochmüllerAna TöpfEce SonmezlerElmasnur YilmazSemra HizUluc YisSerdal GungorAyse Ipek PolatPinar EdemSergi BeltranSteven Laurie*Aysenur YaramisRita HorvathYavuz Oktay

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. Genotypephenotype
correlations remain to be established.

Picture2

Read next...

https://lochmullerlab.org/files/cropped-LochmullerLab_web.jpg

Lochmüller Lab Welcomes New Students

Our lab is growing! We are excited to introduce two new students who have joined the Lochmüller Lab this fall.   Kelly Ho Kelly has...
JND8-4_announcement

Latest Issue of the Journal of Neuromuscular Diseases Now Available – July 2021

The Journal of Neuromuscular Diseases (JND) has announced the publication of a new issue of the journal!     Volume 8, Issue 4 of the JND contains a record number 30 items comprised...
meetClinicalTeam

Meet the Lochmüller Lab Clinical Team

Neuromuscular Clinic for adult patients at The Ottawa Hospital (TOH) Civic Campus As part of the team led by Dr. Jodi Warman Chardon, Hanns sees...
1by1treatabolome

Special issue of the Journal of Neuromuscular Diseases is devoted to the Treatabolome, designed to shorten diagnosis-to-treatment time for patients with rare diseases

In 2019, as part of the European Solve-RD project, Hanns Lochmüller, Gisèle Bonne and Rachel Thompson launched the Treatabolome, an initiative designed to extract details...
ProDGNE RGB-01

ProDGNE: Research Project to Develop an Innovative Therapeutic Compound to Treat GNE Myopathy

The Lochmüller Lab is proud to share its involvement in ProDGNE , a three-year transnational pre-clinical research project which aims to develop an innovative therapeutic...
Neuromuscular junction and animal models

Meet the lab’s two new members

Our lab is growing! We are excited to introduce two new members who have joined the Lochmüller lab this winter. Daniel O'Neil Daniel holds a...