Structural and functional analysis of the human cone‐rod homeobox transcription factor

Clanor, Penelope-Marie; Buchholz, Christine; Hayes, Jonathan E.; Friedman, Michael; White, Andrew M.; Enke, Ray A.; Berndsen, Christopher E.

doi:10.1002/prot.26332

Cited by 9 publications

(4 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, a recent study reported that single CRX whole-gene deletion also causes dominant late-onset macular disease [45]; therefore, further research on this molecular mechanism is required. Mutations within the transactivation domain have no restrictions on the type of mutation due to NMD escape, but mutations that cause large changes, such as truncating mutations, appear to be necessary for most pathological changes [46]. These mutations can appear much more diverse than single-amino-acid substitutions, which may be the cause of more diverse clinical features in the mutations of the transactivation domain than in mutations of the homeodomain in our genotype-phenotype analysis.…”

Section: Discussionmentioning

confidence: 95%

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans

Kim

Joo

Han

et al. 2023

Genes

View full text Add to dashboard Cite

This study aimed to investigate the clinical characteristics of Korean patients with retinal dystrophy associated with pathogenic variants of cone rod homeobox-containing gene (CRX). We retrospectively enrolled Korean patients with CRX-associated retinal dystrophy (CRX-RD) who visited two tertiary referral hospitals. Pathogenic variants were identified using targeted panel sequencing or whole-exome sequencing. We analyzed clinical features and phenotypic spectra according to genotype. Eleven patients with CRX-RD were included in this study. Six patients with cone-rod dystrophy (CORD), two with macular dystrophy (MD), two with Leber congenital amaurosis (LCA), and one with retinitis pigmentosa (RP) were included. One patient (9.1%) had autosomal recessive inheritance, and the other ten patients (90.9%) had autosomal dominant inheritance. Six patients (54.5%) were male, and the mean age of symptom onset was 27.0 ± 17.9 years. At the first presentation, the mean age was 39.4 ± 20.6 years, and best-corrected visual acuity (BCVA) (logMAR) was 0.76 ± 0.90 in the better eye. Negative electroretinography (ERG) was observed in seven (63.6%) patients. Nine pathogenic variants were identified, including two novel variants, c.101-1G>A and c.898T>C:p.(*300Glnext*118). Taken together with the variants reported in prior studies, all variants within the homeodomain are missense variants, whereas most variants downstream of the homeodomain are truncating variants (88%). The clinical features of pathogenic variants within the homeodomain are either CORD or MD with bull’s eye maculopathy, whereas variants downstream of the homeodomain cause more diverse phenotypes, with CORD and MD in 36%, LCA in 40%, and RP in 24%. This is the first case series in Korea to investigate the CRX-RD genotype–phenotype correlation. Pathogenic variants downstream of the homeodomain of the CRX gene are present as RP, LCA, and CORD, whereas pathogenic variants within the homeodomain are mainly present as CORD or MD with bull’s eye maculopathy. This trend was similar to previous genotype–phenotype analyses of CRX-RD. Further molecular biologic research on this correlation is required.

show abstract

Section: Discussionmentioning

confidence: 95%

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans

Kim

Joo

Han

et al. 2023

Genes

View full text Add to dashboard Cite

show abstract

“…Most CRX mutations cause the autosomal dominant form of CORD, accounting for 5-10% of all dominant forms of CORD [26,30,31]. Mutations in CRX genes cause a wide range of retinopathies, including retinitis pigmentosa, conerod dystrophy, and the dominant form of Leber congenital amaurosis, a disorder that is usually autosomal recessive [32,33].…”

Section: Crx Genementioning

confidence: 99%

The Importance of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants in NF1 Gene and CRX Gene. Case Report and Short Literature Review

Jurca,

Petchesi,

Jurca

et al. 2024

Preprint

View full text Add to dashboard Cite

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. A large number of genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant, along with ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually made based on clinical criteria, thus providing patients with competent genetic advice.

show abstract

“…Most CRX mutations cause the autosomal dominant form of CORD, accounting for 5-10% of all dominant forms of CORD [26,27]. Mutations in CRX genes cause a wide range of retinopathies, including retinitis pigmentosa, cone-rod dystrophy, and the dominant form of Leber congenital amaurosis, a disorder that is usually autosomal recessive [28,29].…”

Section: Crx Genementioning

confidence: 99%

The Surprises of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants

Jurca,

Petchesi,

Jurca

et al. 2024

Preprint

View full text Add to dashboard Cite

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

show abstract

Structural and functional analysis of the human cone‐rod homeobox transcription factor

Cited by 9 publications

References 55 publications

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans

The Importance of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants in NF1 Gene and CRX Gene. Case Report and Short Literature Review

The Surprises of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants

Contact Info

Product

Resources

About