FREM1 gene

Overview
Microphthalmia, anophthalmia, coloboma (MAC)
Additional information
References

Overview

Gene (OMIM No.)	FREM1 (#608944)
Function of gene/protein	Protein: FRAS1-related extracellular matrix protein 1 Part of the FRAS/FREM complex, which is vital during embryogenesis The complex is located in cells basement membranes, and plays a role in anchoring cell layers in tissues
Clinical phenotype (OMIM phenotype no.)	Manitoba oculotrichoanal syndrome (#248450) Also known as Marles syndrome Bifid nose with or without anorectal and renal anomalies (#608980) Trigonocephaly 2 (#614485)
Inheritance	Autosomal dominant Autosomal recessive
Ocular features	Microphthalmia, anophthalmia, coloboma (MAC) spectrum Eyelid coloboma Cryptophthalmos (a continuous layer of skin over the eyeball with absent eyelids and palpebral fissures)
Systemic features	Manitoba oculotrichoanal syndrome Aberrant hairline Bifid/broad nasal tip Gastrointestinal anomalies (omphalocele, anal stenosis)
Key investigations	B-scan USS to measure axial length to document microphthalmia Electrophysiology MRI brain and orbit Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosis	Next generation sequencing Targeted gene panels (MAC) Whole genome sequencing
Management	Ocular Management of MAC Input from adnexal and corneal specialists usually required for cryptophthalmos Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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Additional information

The Manitoba oculotrichoanal syndrome was first described by Marles et al in the Oji-Cree Manitoba Indian population residing in an isolated part of northeastern Manitoba, Canada. Subsequent reports of patients from outside this region have been reported since.

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References

Kiyozumi D, Sugimoto N, Sekiguchi K. Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects. Proc Natl Acad Sci. 2006;103(32):11981‐11986
Marles SL, Greenberg CR, Persaud TV, Shuckett EP, Chudley AE. New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians. Am J Med Genet
Yeung A, Amor D, Savarirayan R. Familial upper eyelid coloboma with ipsilateral anterior hairline abnormality: two new reports of MOTA syndrome. Am J Med Genet A. 2009;149A(4):767‐769
Li C, Marles SL, Greenberg CR, et al. Manitoba Oculotrichoanal (MOTA) syndrome: report of eight new cases. Am J Med Genet A. 2007;143A(8):853‐857
Slavotinek AM, Baranzini SE, Schanze D, et al. Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1. J Med Genet. 2011;48(6):375‐382

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Updated on November 30, 2020

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