Congenital cataracts in females caused by BCOR mutations; report of six further families demonstrating clinical variability and diverse genetic mechanisms.
Abnormalities, Multiple
/ genetics
Cataract
/ congenital
Cohort Studies
Databases, Genetic
Female
Genes, X-Linked
Heart Septal Defects
/ diagnosis
Humans
Infant
Infant, Newborn
Microphthalmos
/ diagnosis
Mosaicism
Oligonucleotide Array Sequence Analysis
Pedigree
Phenotype
Point Mutation
Proto-Oncogene Proteins
/ genetics
Rare Diseases
/ genetics
Repressor Proteins
/ genetics
Sequence Analysis, DNA
Sequence Deletion
BCOR
Congenital cataracts
OFCD
Oculofaciocardiodental syndrome
X-linked dominant
Journal
European journal of medical genetics
ISSN: 1878-0849
Titre abrégé: Eur J Med Genet
Pays: Netherlands
ID NLM: 101247089
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
10
12
2018
revised:
26
03
2019
accepted:
28
04
2019
pubmed:
3
5
2019
medline:
21
10
2020
entrez:
4
5
2019
Statut:
ppublish
Résumé
Pathogenic variants in the BCOR gene have been identified in males with X-linked recessive microphthalmia and in females with X-linked dominant oculofaciocardiodental (OFCD) syndrome. This latter condition has previously been regarded as rare but the increased availability of genetic testing in recent years has led to the identification of a greater number of patients. We report the clinical and molecular findings in a series of 10 patients with pathogenic BCOR variants from 5 families, all seen in a single institution over a two year period. We emphasize the phenotypic variability in this cohort and the diverse genetic mechanisms involved which included point mutations and deletions of BCOR as well as the occurrence of gonadal and somatic mosaicism. In this report we demonstrate the novel findings of four newly identified variants in BCOR associated with an OFCD phenotype, and suggest that the frequency of this condition in females presenting with congenital cataract, including unilateral cataract, is more common than anticipated. We demonstrate the utility of screening for genetic causes of congenital cataract. Although gonadal mosaicism in OFCD had previously been reported, we demonstrate the presence of somatic mosaicism where BCOR mutations may only be detected in DNA from tissues other than blood such as buccal cells.
Sections du résumé
BACKGROUND
BACKGROUND
Pathogenic variants in the BCOR gene have been identified in males with X-linked recessive microphthalmia and in females with X-linked dominant oculofaciocardiodental (OFCD) syndrome. This latter condition has previously been regarded as rare but the increased availability of genetic testing in recent years has led to the identification of a greater number of patients.
METHODS
METHODS
We report the clinical and molecular findings in a series of 10 patients with pathogenic BCOR variants from 5 families, all seen in a single institution over a two year period.
RESULTS
RESULTS
We emphasize the phenotypic variability in this cohort and the diverse genetic mechanisms involved which included point mutations and deletions of BCOR as well as the occurrence of gonadal and somatic mosaicism.
CONCLUSION
CONCLUSIONS
In this report we demonstrate the novel findings of four newly identified variants in BCOR associated with an OFCD phenotype, and suggest that the frequency of this condition in females presenting with congenital cataract, including unilateral cataract, is more common than anticipated. We demonstrate the utility of screening for genetic causes of congenital cataract. Although gonadal mosaicism in OFCD had previously been reported, we demonstrate the presence of somatic mosaicism where BCOR mutations may only be detected in DNA from tissues other than blood such as buccal cells.
Identifiants
pubmed: 31048080
pii: S1769-7212(18)30911-X
doi: 10.1016/j.ejmg.2019.04.015
pii:
doi:
Substances chimiques
BCOR protein, human
0
Proto-Oncogene Proteins
0
Repressor Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103658Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.