Sclerocornea–Microphthalmia–Aphakia Complex: Description of Two Additional Cases Associated With Novel FOXE3 Mutations and Review of the Literature

Quiroz-Casian, Natalia; Chacón‐Camacho, Oscar F.; Barragán-Arévalo, Tania; Nava-Valdéz, Jessica; Lieberman, Esther; Salgado-Medina, Acatzin; Navas, Alejandro; Graue-Hernández, Enrique O; Zenteno, Juan Carlos

doi:10.1097/ico.0000000000001655

Cited by 13 publications

(4 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple in silico prediction tools show a damaging effect. This variant has been previously reported in a case with ASD [26]. Therefore, we consider the FOXE3 variant a likely cause of the eye phenotype in our proband.…”

Section: Discussionmentioning

confidence: 51%

Spectrum of Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida

Thanikachalam

Hodapp

Chang

et al. 2020

Genes

View full text Add to dashboard Cite

Anterior segment dysgenesis (ASD) comprises a wide spectrum of developmental conditions affecting the cornea, iris, and lens, which may be associated with abnormalities of other organs. To identify disease-causing variants, we performed exome sequencing in 24 South Florida families with ASD. We identified 12 likely causative variants in 10 families (42%), including single nucleotide or small insertion–deletion variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6. Four variants were novel. Each variant was detected only in one family. Likely causative variants were detected in 1 out of 7 black and 9 out of 17 white families. In conclusion, exome sequencing for ASD allows us to identify a wide spectrum of rare DNA variants in South Florida. Further studies will explore missing variants, especially in the black communities.

show abstract

Section: Discussionmentioning

confidence: 51%

Spectrum of Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida

Thanikachalam

Hodapp

Chang

et al. 2020

Genes

View full text Add to dashboard Cite

show abstract

“…37 To date, 35 pathogenic mutations have been reported in FOXE3 gene including 27 missense, five small deletions and three small insertions (http://www.hgmd.cf.ac.uk/ac/all.php). 25,33,[39][40][41][42][43][44][45][46][47][48][49][50] Most of the missense mutations in FOXE3 gene were reported in the forkhead domain, which acts as a DNA binding domain of FOXE3. These mutations alter the function of DNA binding domain, resulting in reduced transcriptional activation and affecting the normal development of the eye.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia

Akbar,

Ullah,

Haider

et al. 2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

BackgroundAnophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non‐syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non‐genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy. To date, more than 30 genes having different modes of inheritance patterns are identified as causing anophthalmia and microphthalmia.MethodsIn the present study, a clinical and genetic analysis was performed of six patients with anophthalmia and microphthalmia and/or additional phenotypes of intellectual disability, developmental delay and cerebral palsy from a large consanguineous Pakistani family. Whole exome sequencing followed by data analysis for variants prioritization and validation through Sanger sequencing was performed to identify the disease causing variant(s). American College of Medical Genetics and Genomics (ACMG) guidelines were applied to classify clinical interpretation of the prioritized variants.ResultsClinical investigations revealed that the affected individuals are afflicted with anophthalmia. Three of the patients showed additional phenotype of intellectual disability, developmental delays and other neurological symptoms. Whole exome sequencing of the DNA samples of the affected members in the family identified a novel homozygous stop gain mutation (NM_012186: c.106G>T: p.Glu36*) in Forkhead Box E3 (FOXE3) gene shared by all affected individuals. Moreover, patients segregating additional phenotypes of spastic paraplegia, intellectual disability, hearing loss and microcephaly showed an additional homozygous sequence variant (NM_004722: c.953G>A: p.Arg318Gln) in AP4M1. Sanger sequencing validated the correct segregation of the identified variants in the affected family. ACMG guidelines predicted the variants to be pathogenic.ConclusionsWe have investigated first case of syndromic anophthalmia caused by variants in the FOXE3 and AP4M1. The present findings are helpful for understanding pathological role of the mutations of the genes in syndromic forms of anophthalmia. Furthermore, the study signifies searching for the identification of second variant in families with patients exhibiting variable phenotypes. In addition, the findings will help clinical geneticists, genetic counselors and the affected family with respect to prenatal testing, family planning and genetic counseling.

show abstract

“… 36 It can be isolated or associated with additional ocular and systemic anomalies. 37 It is generally associated with a poor prognosis requiring repeated regrafts. 38 …”

Section: Congenital Opacitiesmentioning

confidence: 99%

Pediatric corneal transplantation: techniques, challenges, and outcomes

Gurnani,

Kaur,

Chaudhary

et al. 2024

Ophthalmol Eye Dis

View full text Add to dashboard Cite

Pediatric corneal transplant is a highly demanding and technically challenging procedure for the cornea surgeon in today’s era. These cases pose unique challenges in clinical and surgical management. The indications of pediatric corneal transplant can be therapeutic, tectonic, optical, and cosmetic. Pediatric patients undergoing corneal transplants are at a high risk of graft infection, failure, rejection, dehiscence, and amblyopia due to young age, robust immune system, increased incidence of trauma, and compliance issues. The other factors contributing to graft failure can be allograft rejection, secondary glaucoma, corneal vascularization, multiple surgeries, vitreous prolapse, and lack of treatment compliance. A successful corneal transplant in children depends on meticulous preoperative evaluation, uneventful surgery, the expertise of a corneal surgeon, and regular and timely postoperative follow-up. Therapeutic and optical penetrating keratoplasty are the most commonly performed transplants in children. However, with the advancements in surgical technique and management protocol, the current focus has shifted toward lamellar keratoplasty. Lamellar keratoplasty offers early visual recovery and potentially fewer complications. Visual rehabilitation through corneal transplant in otherwise blind eyes can be a boon for the children. Recently, keratoprostheses have been promising in children with multiple graft failures. The current review gives insights into epidemiology, etiology, indications, clinical characteristics, investigations, management options, recent advances, and the future of pediatric corneal transplants. As surgical techniques continue to grow and comprehension of pediatric corneal transplants is improving, we can safeguard these eyes with the best possible anatomical and functional outcomes.

show abstract

Sclerocornea–Microphthalmia–Aphakia Complex: Description of Two Additional Cases Associated With Novel FOXE3 Mutations and Review of the Literature

Cited by 13 publications

References 9 publications

Spectrum of Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida

Spectrum of Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia

Pediatric corneal transplantation: techniques, challenges, and outcomes

Contact Info

Product

Resources

About