PT  - JOURNAL ARTICLE
AU  - Abolfazl Rad
AU  - Umut Altunoglu
AU  - Rebecca Miller
AU  - Reza Maroofian
AU  - Kiely N James
AU  - Ahmet Okay Çağlayan
AU  - Maryam Najafi
AU  - Valentina Stanley
AU  - Rose-Mary Boustany
AU  - Gözde Yeşil
AU  - Afsaneh Sahebzamani
AU  - Gülhan Ercan-Sencicek
AU  - Kolsoum Saeidi
AU  - Kaman Wu
AU  - Peter Bauer
AU  - Zeineb Bakey
AU  - Joseph G Gleeson
AU  - Natalie Hauser
AU  - Murat Gunel
AU  - Hulya Kayserili
AU  - Miriam Schmidts
TI  - MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive <em>c</em>erebellar, <em>o</em>cular, cranio<em>f</em>acial and <em>g</em>enital features (COFG syndrome)
AID  - 10.1136/jmedgenet-2018-105623
DP  - 2019 May 01
TA  - Journal of Medical Genetics
PG  - 332--339
VI  - 56
IP  - 5
4099  - http://jmg.bmj.com/content/56/5/332.short
4100  - http://jmg.bmj.com/content/56/5/332.full
SO  - J Med Genet2019 May 01; 56
AB  - 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.