POMT1 gene

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

Overview

Gene (OMIM No.)	POMT1 (#607423)
Function of gene/protein	Protein: protein O-mannosyltransferase 1 (POMT1) POMT1 is part of the POMT enzyme complex which is involved in the glycosylation of alpha-dystroglycan (DAG1) DAG1 helps maintain tissue structure in skeletal muscles and the brain
Clinical phenotype (OMIM phenotype no.)	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (#236670) Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB) Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (#613155) Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (#609308) Defects in the glycosylation of alpha-dystroglycans cause 3 overlapping syndromes/dystroglycanopathies: WWS, MEB and Fukuyama type Congenital Muscular Dystrophy (FCMD; (#253800) WWS—most severe phenotype; MEB—intermediate phenotype; FCMD—mildest phenotype Phenotype severity is determined by the extent which the mutation affects DAG1 glycosylation
Inheritance	Autosomal recessive
Ocular features	Microphthalmia, anophthalmia, coloboma (MAC) spectrum Congenital cataracts Anterior segment dysgenesis Congenital glaucoma Persistent foetal vasculature Retinal dysplasia Retinal detachment Optic atrophy High myopia
Systemic features	Congenital muscular dystrophy Brain anomalies (cobblestone lissencephaly, hydrocephalus, hypoplastic cerebellar vermis, macrocephaly, microcephaly or anencephaly) Severe hypotonia Occasional seizures Intellectual disability Developmental delays Patients with WWS have a severely limited lifespan with significant CNS and ocular anomalies
Key investigations	B-scan USS to measure axial length to document microphthalmia Electrophysiology to determine visual potential Measurement of intraocular pressure Gonioscopy (if tolerated/EUA) or anterior segment OCT to identify angle abnormalities and any associated anterior segment dysgenesis MRI brain and orbit Systemic assessment with a paediatrician and other relevant specialists Bloods (elevated creatinine kinase) Skeletal muscle biopsy
Molecular diagnosis	Next generation sequencing Targeted gene panels Whole genome sequencing
Management	Ocular Management of MAC Management of congenital cataract Management of anterior segment dysgenesis Management of congenital glaucoma Surgery for dysplastic retina does not confer any visual benefit Rhegmatogenous retinal detachment associated with MEB may be amenable to scleral buckling or vitrectomies Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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References

Manya H, Chiba A, Yoshida A, et al. Demonstration of mammalian protein O-mannosyltransferase activity: Coexpression of POMT1 and POMT2 required for enzymatic activity. Proc Natl Acad Sci U S A 2004; 101: 500–505
Akasaka-Manya K, Manya H, Endo T. Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation. Biochem Biophys Res Commun 2004; 325: 75–79
Akasaka-Manya K, Manya H, Nakajima A, et al. Physical and functional association of human protein O-mannosyltransferases 1 and 2. J Biol Chem 2006; 281: 19339–19345
Beltrán-Valero De Bernabé D, Currier S, Steinbrecher A, et al. Mutations in the O-Mannosyltransferase Gene POMT1 Give Rise to the Severe Neuronal Migration Disorder Walker-Warburg Syndrome. Am J Hum Genet 2002; 71: 1033–1043
Kim DS, Hayashi YK, Matsumoto H, et al. POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG. Neurology 2004; 62: 1009–1011
Francisco R, Pascoal C, Marques-da-Silva D, et al. Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review. J Inherit Metab Dis. 2019;42(1):29-48

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Updated on November 30, 2020

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