Journal Article

Expanding the phenotype of the X-linked BCOR microphthalmia syndromes


Two distinct syndromes arise from pathogenic variants in the X-linked gene BCOR (BCL-6 corepressor): oculofaciocardiodental (OFCD) syndrome, which affects females, and a severe microphthalmia (‘Lenz’-type) syndrome affecting males. OFCD is an X-linked dominant syndrome caused by a variety of BCOR null mutations. As it manifests only in females, it is presumed to be lethal in males. The severe male X-linked recessive microphthalmia syndrome (‘Lenz’) usually includes developmental delay in addition to the eye findings and is caused by hypomorphic BCOR variants, mainly by a specific missense variant c.254C > T, p.(Pro85Leu). Here, we detail 16 new cases (11 females with 4 additional, genetically confirmed, affected female relatives; 5 male cases each with unaffected carrier mothers). We describe new variants and broaden the phenotypic description for OFCD to include neuropathy, muscle hypotonia, pituitary underdevelopment, brain atrophy, lipoma and the first description of childhood lymphoma in an OFCD case. Our male X-linked recessive cases show significant new phenotypes: developmental delay (without eye anomalies) in two affected half-brothers with a novel BCOR variant, and one male with high myopia, megalophthalmos, posterior embryotoxon, developmental delay, and heart and bony anomalies with a previously undescribed BCOR splice site variant. Our female OFCD cases and their affected female relatives showed variable features, but consistently had early onset cataracts. We show that a mosaic carrier mother manifested early cataract and dental anomalies. All female carriers of the male X-linked recessive cases for whom genetic confirmation was available showed skewed X-inactivation and were unaffected. In view of the extended phenotype, we suggest a new term of X-linked BCOR-related syndrome.

Attached files


Ragge, Nicola
Isidor, Bertrand
Bitoun, Pierre
OdentIrina Giurgea, Sylvie
Cogné, Benjamin
Deb, Wallid
Marie, Vincent
Le Gall, Jessica
Morton, Jenny
Lim, Derek
Le Meur, Guylène
Zazo Seco, Celia
Zafeiropoulou, Dimitra
Bax, Dorine
Zwijnenburg, Petra
Arteche, Anara
Tahsin Swafiri , Saoud
Cleaver, Ruth
McEntagart, Meriel
Kini, Usha
Newman, William
Ayuso, Carmen
Corton, Marta
Herenger, Yvan
Jeanne, Médéric
Calvas, Patrick
Chassaing, Nicolas

Oxford Brookes departments

Faculty of Health and Life Sciences


Year of publication: 2018
Date of RADAR deposit: 2018-07-09

Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

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