Complete Aniridia with Central Keratopathy and Congenital Glaucoma is a<i>CYP1B1-</i>related Phenotype

Khan, Arif O.; Aldahmesh, Mohammed A.; Mohamed, Jawahir Y.; Hijazi, Hadia; Alkuraya, Fowzan S.

doi:10.3109/13816810.2013.804096

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…Its increased expression in fetal eyes as compared to adult eyes suggests its significance in the development of childhood glaucoma specifically [190]. Numerous case reports have highlighted the incidence of bilateral PCG in those with homozygous or compound heterozygous CYP1B1 variants in individuals both with and without a family history of the disease, with the most common variants being p.G61E, p.R368H, pE229K, and p.R390H [26][27][28][29][30][31][32][33][34][35][36].…”

Section: Cyp1b1mentioning

confidence: 99%

Genetic changes and testing associated with childhood glaucoma: A systematic review

Kumar,

Han,

Oatts

2024

PLoS ONE

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Many forms of childhood glaucoma have been associated with underlying genetic changes, and variants in many genes have been described. Currently, testing is variable as there are no widely accepted guidelines for testing. This systematic review aimed to summarize the literature describing genetic changes and testing practices in childhood glaucoma. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) 2020 guidelines and registered with Prospero (ID CRD42023400467). A comprehensive review of Pubmed, Embase, and Cochrane databases was performed from inception through March 2, 2023 using the search terms: (glaucoma) AND (pediatric OR childhood OR congenital OR child OR infant OR infantile) AND (gene OR genetic OR genotype OR locus OR genomic OR mutation OR variant OR test OR screen OR panel). Information was extracted regarding genetic variants including genotype-phenotype correlation. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1,916 records screened, 196 studies met inclusion criteria and 53 genes were discussed. Among study populations, mean age±SD at glaucoma diagnosis was 8.94±9.54 years and 50.4% were male. The most common gene discussed was CYP1B1, evaluated in 109 (55.6%) studies. CYP1B1 variants were associated with region and population-specific prevalence ranging from 5% to 86% among those with primary congenital glaucoma. MYOC variants were discussed in 31 (15.8%) studies with prevalence up to 36% among patients with juvenile open angle glaucoma. FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation. Overall risk of bias was low; the most common domains of bias were selection and comparability. Numerous genes and genetic changes have been associated with childhood glaucoma. Understanding the most common genes as well as potential genotype-phenotype correlation has the potential to improve diagnostic and prognostic outcomes for children with glaucoma.

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Section: Cyp1b1mentioning

confidence: 99%

Genetic changes and testing associated with childhood glaucoma: A systematic review

Kumar,

Han,

Oatts

2024

PLoS ONE

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“…106210: ANIRIDIA; AN 194072: WILMS TUMOR, ANIRIDIA, GENITOURI-NARYANOMALIES, AND MENTAL RETARDATION SYNDROME; WAGR 206700: ANIRIDIA, CEREBELLAR ATAXIA, AND MENTAL RETARDATION (GILLESPIE SYNDROME) 607108: PAIRED BOX GENE 6; PAX6 PAX6-associated aniridia is a profound pan-ocular developmental disorder of the eyes, the consequences of which can lead to blindness during the course of life, especially due to secondary glaucoma (Khan et al 2014;Viestenz et al 2017). Also, there are often systemic manifestations in PAX6 syndrome with metabolic and neurological alterations.…”

Section: Omim Entries For Aniridiamentioning

confidence: 99%

“…PAX6 syndrome (OMIM 106210, ORPHA77) has panocular and progressive manifestations (macular and optic hypoplasia, corneal opacifications, cataract, glaucoma, progressive scar formation) and often systemic involvement (early onset diabetes, disturbance of diurnal rhythms, cerebral malformations, auditory abnormalities, renal insufficiency) (Bamiou et al 2007;Ihnatko et al 2013Ihnatko et al , 2016. There is congenital visual impairment with progressive loss of vision mainly due to the negative effects of limbal stem cell insufficiency (LSCI) (Gregory-Evans et al 2011;Khan et al 2014;Lagali et al 2013;Le et al 2013;Netland et al 2011).…”

Section: Basics Of Limbal Stem Cell Insufficiency In Pax6-related Animentioning

confidence: 99%

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Diagnostic impact of anterior segment angiography of limbal stem cell insufficiency in PAX6‐related aniridia

et al. 2018

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PAX6 is a master gene of ocular development and postnatal ocular equilibrium. Congenital aniridia is the hallmark of PAX6 gene haploinsufficiency (Chr. 11 p. 13), but PAX6-associated aniridia is a profound, progressive pan-ocular developmental disorder often leading to blindness. There is congenital visual impairment with advancing loss of vision mainly due to secondary glaucoma and to corneal blindness caused by limbal stem cell insufficiency (LSCI). LSCI leads to ARK (aniridia-related keratopathy), which typically develops in four stages. Incipient LSCI with vessels starting to grow into the cornea can be imaged by fluorescein anterior segment angiography, which enables fine vessels to be more easily detected than by routine slit lamp examination, especially in patients with nystagmus. Thus, clinical stage 1 ARK is often diagnosed at stage 2 by angiography. Corneal neovascularizations often start at the 12 and 6 positions and subsequently progress circumferentially, not at the 3 and 9 positions as previously believed. Anterior segment angiography can provide an easily standardizable tool for monitoring progress, treatment-induced regress or stabilization of ARK. Especially in children, angiography could be used to monitor new treatment regimens for reducing LSCI. Angiography could enable treatment to begin earlier to preserve corneal hemostasis. In addition, the fact that vascularization often starts at the subpalpebral 6 and 12 positions as opposed to the 3 and 9 positions raises more questions concerning factors that promote LSCI and related corneal injuries. Clin. Anat. 31:392-397, 2018. © 2018 Wiley Periodicals, Inc.

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“…The inheritance is mainly autosomal dominant with high penetrance but variable expressivity. Other genes, such as FOXC1, CYP1B1, PITX2 and FOXE3, have been reported to be associated with iris hypoplasia or aniridia-like phenotype (Ito et al, 2009;Khan et al, 2011a;Khan et al, 2008;Khan et al, 2014;Law et al, 2011;Semina et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis by NGS and MLPA in Chinese Aniridia Patients

Wang

et al. 2023

Preprint

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Purpose: To report clinical features and elucidate genetic etiology of patients with congenital aniridia and to reveal the mutational spectrum in the Chinese population. Methods: Sixty patients with congenital aniridia from 51 families were recruited in this study. Candidate genes of developmental eye diseases were captured and analyzed by panel-based next-generation sequencing (NGS), and the mutations were confirmed by polymerase chain reaction (PCR) and Sanger sequencing. Multiplex ligation probe amplification (MLPA)of PAX6 and FOXC1 was performed to detect copy number variations (CNVs) for patients without intragenic mutations. Results: Clinical examinations revealed that 58 patients had complete iris loss, two patients showed partial iris loss. Two patients were diagnosed WAGR syndrome with nephroblastoma. Combining panel-based NGS and MLPA, 43 intragenic mutations or deletions of PAX6, FOXC1, and BCOR genes were identified in 59 patients, including 33 point-mutations (76.7%) in 43 patients and 10 deletions (23.3%) in 16 patients; the total detection rate was 98.3%. Phenotypic variations were observed between families and intra-families. Conclusion: The results confirmed that variations in PAX6 and adjacent regions were the predominant cause of aniridia in China. Besides intragenic point mutations in PAX6, the deletion comprising PAX6 gene or the adjacent genes is also a common cause of congenital aniridia. In addition, FOXC1 gene is another important gene causing congenital aniridia. Panel-based NGS combined with MLPA increase significantly the detection rate of gene mutations for patients with congenital aniridia.

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Complete Aniridia with Central Keratopathy and Congenital Glaucoma is aCYP1B1-related Phenotype

Cited by 9 publications

References 9 publications

Genetic changes and testing associated with childhood glaucoma: A systematic review

Genetic changes and testing associated with childhood glaucoma: A systematic review

Diagnostic impact of anterior segment angiography of limbal stem cell insufficiency in PAX6‐related aniridia

Genetic Analysis by NGS and MLPA in Chinese Aniridia Patients

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