Novel CHRDL1 mutation causing X-linked megalocornea in a family with mild anterior segment manifestations in carrier females.
Ophthalmic Genet
; 43(2): 224-229, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-34844512
ABSTRACT
PURPOSE:
X-linked megalocornea (XMC) is a rare anterior segment malformation characterized by a nonprogressive enlargement of the cornea to 13 mm or greater in the setting of normal intraocular pressure. XMC is caused by mutations in the CHRDL1 gene and it is inherited as an X-linked recessive trait affecting only males. Here, we describe the results of phenotypic and genetic assessment in a novel XMC pedigree.METHODS:
Three subjects (a father and his two daughters) underwent a complete clinical and imaging ocular examination including biomicroscopy, fundoscopy, tonometry, visual acuity, Pentacam Scheimpflug imaging, anterior segment Swept Source OCT, and ultrabiomicroscopy. Genetic analysis was performed through whole exome sequencing in 3 family members. Candidate variants were validated by sanger sequencing.RESULTS:
The affected father exhibited megalocornea, very deep anterior chambers, retrocorneal pigmentation, iris atrophy, queer iris configuration, extremely open iridocorneal angles, and cataracts. Notably, both daughters showed queer iris configuration and abnormally widely open iridocorneal angles in both eyes. Genetic analysis identified a novel hemizygous c.207+1G>A splicing variant in CHRDL1 in the affected father. Both mildly affected daughters were heterozygous for the pathogenic variant.CONCLUSIONS:
Here, we report an additional XMC family due to a novel mutation in the CHRDL1 gene. Mild anterior segment anomalies were observed in two heterozygous carriers demonstrating for the first time a CHRDL1-linked phenotype in females. A detailed comparison of the clinical and genetic features of this pedigree with those observed in previously published XMC cases is also presented.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oftalmopatias Hereditárias
/
Doenças Genéticas Ligadas ao Cromossomo X
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Ophthalmic Genet
Assunto da revista:
GENETICA MEDICA
/
OFTALMOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
México