Related Experiment Video
Updated: Jun 25, 2026
Modeling Posthemorrhagic Hydrocephalus of Prematurity in Rats
Published on: March 28, 2025
COL4A1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage
Linda S de Vries1, Corine Koopman, Floris Groenendaal
1Department of Neonatology, Wilhelmina Children's Hospital, UMC Utrecht, the Netherlands. l.s.devries@umcutrecht.nl
Insights
A mutation in the collagen 4 A1 (COL4A1) gene is linked to brain abnormalities like intracerebral hemorrhage and porencephaly in preterm infants. This genetic factor may increase the risk of these conditions at birth.
Area of Science:
- Genetics
- Neurology
- Neonatology
Background:
- Intracerebral hemorrhage and porencephaly are serious conditions affecting newborns.
- The role of specific gene mutations in congenital brain malformations requires further investigation.
Purpose of the Study:
- To identify genetic causes of congenital intracerebral hemorrhage and porencephaly.
- To report a novel mutation in the collagen 4 A1 (COL4A1) gene associated with these conditions in preterm infants.
Main Methods:
- Neurological, ophthalmological, and magnetic resonance imaging (MRI) evaluations were performed on two preterm infants and their family members.
- Mutation analysis of the COL4A1 gene was conducted in affected infants and their mother.
Main Results:
- A novel G1580R mutation in the COL4A1 gene was identified in both preterm infants.
- Intracerebral hemorrhage and porencephaly were diagnosed in the infants, with leukoencephalopathy noted in other family members.
- The infants were asymptomatic at birth, with abnormalities detected via ultrasound and confirmed by MRI.
Conclusions:
- Mutation of the COL4A1 gene is implicated as a risk factor for antenatal intracerebral hemorrhage and subsequent porencephaly in preterm newborns.
- This finding highlights the importance of genetic screening in cases of congenital brain malformations.
Objective:
To report the presence of intracerebral hemorrhage and porencephaly, both present at birth, in two preterm infants with a mutation in the collagen 4 A1 gene.
Methods:
Two preterm infants with antenatal intracerebral hemorrhage and established porencephaly, as well as their affected mother and grandfather, underwent neurological and ophthalmological examination and magnetic resonance imaging of the brain. Mutation analysis of the COL4A1 gene was performed in the infants and in their mother.
Results:
Both infants had a novel G1580R mutation in the COL4A1 gene, encoding procollagen type IV alpha1. A history of mild antenatal trauma was present in the first but not in the second infant. Both preterm infants were asymptomatic at birth. The intracerebral hemorrhage and porencephaly were diagnosed with cranial ultrasound examination and were subsequently confirmed with magnetic resonance imaging. Leukoencephalopathy was present in the mother and in her father.
Interpretation:
Mutation of the COL4A1 gene appears to be a risk factor of antenatal intracerebral hemorrhage followed by porencephaly in the preterm newborn.
Related Concept Videos
01:17Hemorrhagic Stroke l: Introduction
01:29Hemorrhagic Stroke ll: Pathophysiology
01:05Type IV Collagen of Basal Lamina
A type IV collagen molecule has six alpha chains which can exist in...