MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome)
Abstract: Background Putative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including the eye, midbrain, neural tube and reproductive organs. Objective A homozygous truncating variant in MAB21L1 has recently been described in a male affected by intellectual disability, scrotal agenesis, ophthalmological anomalies, cerebellar hypoplasia and facial dysmorphism. We employed a combination of exome sequencing and homozygosity mapping to identify the underlying genetic cause in subjects with similar phenotypic features descending from five unrelated consanguineous families. Results We identified four homozygous MAB21L1 loss of function variants (p.Glu281fs*20, p.Arg287Glufs*14 p.Tyr280* and p.Ser93Serfs*48) and one missense variant (p.Gln233Pro) in 10 affected individuals from 5 consanguineous families with a distinctive autosomal recessive neurodevelopmental syndrome. Cardinal features of this syndrome include a characteristic facial gestalt, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds and scrotum/ scrotal agenesis as well as cerebellar hypoplasia with ataxia and variable microcephaly. Conclusion This report defines an ultrarare but clinically recognisable Cerebello-Oculo-Facio-Genital syndrome associated with recessive MAB21L1 variants. Additionally, our findings further support the critical role of MAB21L1 in cerebellum, lens, genitalia and as craniofacial morphogenesis
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Journal of medical genetics. - 56, 5 (2019) , 332-339, ISSN: 1468-6244
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2019
- Creator
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Rad, Abolfazl
Altunoglu, Umut
Miller, Rebecca
Maroofian, Reza
James, Kiely N.
Çağlayan, Ahmet Okay
Najafi, Maryam
Stanley, Valentina
Boustany, Rose-Mary
Yeşil, Gözde
Sahebzamani, Afsaneh
Ercan-Sencicek, Gülhan
Saeidi, Kolsoum
Wu, Kaman
Bauer, Peter
Bakey, Zeineb
Gleeson, Joseph G.
Hauser, Natalie
Gunel, Murat
Kayserili, Hulya
Schmidts, Miriam
- DOI
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10.1136/jmedgenet-2018-105623
- URN
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urn:nbn:de:bsz:25-freidok-1505979
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:36 AM CEST
Data provider
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Associated
- Rad, Abolfazl
- Altunoglu, Umut
- Miller, Rebecca
- Maroofian, Reza
- James, Kiely N.
- Çağlayan, Ahmet Okay
- Najafi, Maryam
- Stanley, Valentina
- Boustany, Rose-Mary
- Yeşil, Gözde
- Sahebzamani, Afsaneh
- Ercan-Sencicek, Gülhan
- Saeidi, Kolsoum
- Wu, Kaman
- Bauer, Peter
- Bakey, Zeineb
- Gleeson, Joseph G.
- Hauser, Natalie
- Gunel, Murat
- Kayserili, Hulya
- Schmidts, Miriam
- Universität
Time of origin
- 2019