COL4A1 gene

Overview
Microphthalmia, anophthalmia, coloboma (MAC)
Anterior segment dysgenesis
Congenital cataract
References

Overview

Gene (OMIM No.)	COL4A1 (#120130)
Function of gene/protein	Protein: collagen, type IV, alpha-1 chain A component of type IV collagen, a flexible protein important for the structure of many tissues Type IV collagen is the main component of cell basement membranes, particularly in blood vessels Helps maintain structural stability of the basement membrane and facilitates interaction with surrounding cells (cell movement, growth, maturation and survival)
Clinical phenotype (OMIM phenotype no.)	Brain small vessel disease with or without ocular anomalies (#175780) Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps (#611773) Hemorrhage, intracerebral, susceptibility to (#614519) Microangiopathy and leukoencephalopathy, pontine, autosomal dominant (#618564)
Inheritance	Autosomal dominant
Ocular features	Microphthalmia, anophthalmia, coloboma (MAC) spectrum Anterior segment dysgenesis Congenital cataract Secondary glaucoma Retinal vascular pathologies
Systemic features	Brain small vessel disease with or without ocular anomalies: Cerebrovascular disease (stroke, transient ischaemia attacks) Leukoencephalopathy (brain white-matter diseases) Proencephaly (cystic cerebral cavities that communicate with ventricles) Resulting in a range of neurological consequences with variable severity within and between families
Key investigations	B-scan USS to measure axial length to document microphthalmia and detect posterior segment abnormalities Electrophysiology MRI brain and orbit Systemic assessment by a paediatrician/stroke physician/neurologist depending on age
Molecular diagnosis	Next generation sequencing Targeted gene panels (MAC/ASD) Whole genome sequencing
Management	Ocular Management of MAC Management of anterior segment dysgenesis Management of congenital cataract Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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References

Bhave G, Colon S, Ferrell N. The sulfilimine cross-link of collagen IV contributes to kidney tubular basement membrane stiffness. Am J Physiol Renal Physiol. 2017;313(3):F596‐F602
Colorado PC, Torre A, Kamphaus G, et al. Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res. 2000;60(9):2520‐2526
Gould DB, Phalan FC, van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354(14):1489‐1496
Merello E, Swanson E, De Marco P, et al. No major role for the EMX2 gene in schizencephaly. Am J Med Genet A. 2008;146A(9):1142‐1150
Shah S, Ellard S, Kneen R, et al. Childhood presentation of COL4A1 mutations. Dev Med Child Neurol. 2012;54(6):569‐574
van der Knaap MS, Smit LM, Barkhof F, et al. Neonatal porencephaly and adult stroke related to mutations in collagen IV A1. Ann Neurol. 2006;59(3):504‐511
Yoneda Y, Haginoya K, Kato M, et al. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann Neurol. 2013;73(1):48‐57
Coupry I, Sibon I, Mortemousque B, Rouanet F, Mine M, Goizet C. Ophthalmological features associated with COL4A1 mutations. Arch Ophthalmol. 2010;128(4):483‐489
Kuo DS, Labelle-Dumais C, Gould DB. COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. Hum Mol Genet. 2012;21(R1):R97‐R110

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Updated on November 30, 2020

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