Axial Length Distributions in Patients With Genetically Confirmed Inherited Retinal Diseases

Williams, Katie; Georgiou, Michalis; Kalitzeos, Angelos; Chow, Isabelle; Hysi, Pirro G.; Robson, Anthony G.; Lingham, Gareth; Chen, Fred K.; Mackey, David A.; Webster, Andrew R.; Hammond, Christopher J; Prokhoda, Polina; Carroll, Joseph; Michaelides, Michel; Mahroo, Omar A.

doi:10.1167/iovs.63.6.15

Cited by 13 publications

(6 citation statements)

References 53 publications

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“…The proband in this study, in addition to the typical clinical phenotypes of OA1, was also complicated with high myopia. It has been found from some studies that, unlike the TYR gene-related albinism, GPR143 gene-related albinism is more likely to be complicated with a short ocular axis [ 44 ]. In 2022, Pavan Verkicharla analyzed the refractive status of 618 albinos and found that high myopia being much more prevalent than hyperopia [ 45 ], suggesting that high myopia is also a common sign in albinism, and that if patients are complicated with high myopia, then, as in this case, albinism-like fundus changes are often less typical, so that OA1 is often misdiagnosed as idiopathic congenital nystagmus [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Novel mutations of the X-linked genes associated with early-onset high myopia in five Chinese families

Zi,

Li,

Cheng

et al. 2023

BMC Med Genomics

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Purpose To report novel pathogenic variants of X-linked genes in five Chinese families with early-onset high myopia (eoHM) by using whole-exome sequencing and analyzing the phenotypic features. Methods 5 probands with X-linked recessive related eoHM were collected in Ningxia Eye Hospital from January 2021 to June 2022. The probands and their family members received comprehensive ophthalmic examinations,and DNA was abstracted from patients and family members. Whole-exome sequencing was performed on probands to screen the causative variants, and all suspected pathogenic variants were determined by Sanger sequencing and co-segregation analysis was performed on available family members. The pathogenicity of novel variants was predicted using silico analysis and evaluated according to ACMG guidelines. RT-qPCR was used to detect differences in the relative mRNAs expression of candidate gene in mRNAs available with the proband and family members in the pedigree 2. The relationship between genetic variants and clinical features was analyzed. Results All probands were male, and all pedigrees conformed to an X-linked recessive inheritance pattern. They were diagnosed with high myopia at their first visits between 4 and 7 years old. Spherical equivalent ranged between − 6.00D and − 11.00D.The five novel hemizygous variants were found in the probands, containing frameshift deletion variant c.797_801del (p.Val266Alafs*75) of OPN1LW gene in the pedigree 1, nonsense variant c.513G > A (p.Trp171Ter)of RP2 gene in the pedigree 2, missense variant c.98G > T (p.Cys33Phe) of GPR143 gene in the pedigree 3, frameshift deletion variant c.1876_1877del (p.Met626Valfs*22) of FRMD7 gene in the pedigree 4 and inframe deletion variant c.670_ 675del (p.Glu192_ Glu193del) of HMGB3 gene in the pedigree 5. All variants were classified as pathogenic or likely pathogenic by the interpretation principles of HGMD sequence variants and ACMG guidelines. In family 2, RT-qPCR showed that the mRNA expression of RP2 gene was lower in the proband than in other normal family members, indicating that such variant caused an effect on gene function at the mRNA expression level. Further clinical examination showed that pedigrees 1, 2, 3, and 4 were diagnosed as X-linked recessive hereditary eye disease with early-onset high myopia, including quiescent cone dysfunction, retinitis pigmentosa, ocular albinism, and idiopathic congenital nystagmus respectively. The pedigree 5 had eoHM in the right eye and ptosis in both eyes. Conclusion In this paper,we are the first to report five novel hemizygous variants in OPN1LW, RP2, GPR143, FRMD7, HMGB3 genes are associated with eoHM. Our study extends the genotypic spectrums for eoHM and better assists ophthalmologists in assessing, diagnosing, and conducting genetic screening for eoHM.

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Section: Discussionmentioning

confidence: 99%

Novel mutations of the X-linked genes associated with early-onset high myopia in five Chinese families

Zi,

Li,

Cheng

et al. 2023

BMC Med Genomics

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“…106 Refractive error also provides clues to inherited retinal disorders and underlying genetic aetiology. 107 Myopia maybe the only ocular feature or part of a more complex ocular or clinical phenotype. 108 Genetic tests have the potential to not only enhance diagnostic precision but also provide targets for cutting edge genetic therapies.…”

Section: Geneticsmentioning

confidence: 99%

“…Refractive error also provides clues to inherited retinal disorders and underlying genetic aetiology 107 . Myopia maybe the only ocular feature or part of a more complex ocular or systemic clinical phenotype 108 …”

Section: Geneticsmentioning

confidence: 99%

Managing the apparently blind child presenting in the first year of life: A review

Leahy,

Lo‐Cao,

Jamieson

et al. 2024

Clinical Exper Ophthalmology

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Severe vision impairment and blindness in childhood have a significant health burden on the child, family and society. This review article seeks to provide a structured framework for managing the apparently blind child presenting in the first year of life, starting from a comprehensive history and examination. Different investigation modalities and the increasingly important role of genetics will also be described, in addition to common causes of severe vision impairment. Crucially, a systematic approach to the blind infant is key to correct diagnoses and timely management. Incorrect diagnoses can be costly to all involved, however it is important to note that diagnoses can change with ongoing follow‐up and investigations. Furthermore, the modern age of ophthalmology requires a multi‐disciplinary approach and close collaboration with specialists including paediatricians, neurologists and geneticists, in addition to rehabilitation and low vision services, to ensure the best care for these vulnerable infants.

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“… 23 , 48 An analysis of a large group of genetically characterized patients with inherited retinal disease has demonstrated that four genetic subtypes, blue cone monochromacy, Bornholm eye disease (both associated with OPN1LW and OPN1MW or their regulatory regions), and retinal dystrophies caused by RPGR and RPE65 mutations were associated with increased axial length. 49 Two genes associated with albinism (such as OCA2 and TYR ) also increased the risk of longer axial length. Short axial lengths are also seen in certain gene variants.…”

Section: Etiology Of High Myopia In Childrenmentioning

confidence: 99%

IMI—Management and Investigation of High Myopia in Infants and Young Children

Flitcroft

Ainsworth

Chia

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤−6 diopters [D]) in infants and young children. Findings High myopia is rare in pre-school children with a prevalence less than 1%. The etiology of myopia in such children is different than in older children, with a high rate of secondary myopia associated with prematurity or genetic causes. The priority following the diagnosis of high myopia in childhood is to determine whether there is an associated medical diagnosis that may be of greater overall importance to the health of the child through a clinical evaluation that targets the commonest features associated with syndromic forms of myopia. Biometric evaluation (including axial length and corneal curvature) is important to distinguishing axial myopia from refractive myopia associated with abnormal development of the anterior segment. Additional investigation includes ocular imaging, electrophysiological tests, genetic testing, and involvement of pediatricians and clinical geneticists is often warranted. Following investigation, optical correction is essential, but this may be more challenging and complex than in older children. Application of myopia control interventions in this group of children requires a case-by-case approach due to the lack of evidence of efficacy and clinical heterogeneity of high myopia in young children. Conclusions High myopia in infants and young children is a rare condition with a different pattern of etiology to that seen in older children. The clinical management of such children, in terms of investigation, optical correction, and use of myopia control treatments, is a complex and often multidisciplinary process.

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Axial Length Distributions in Patients With Genetically Confirmed Inherited Retinal Diseases

Cited by 13 publications

References 53 publications

Novel mutations of the X-linked genes associated with early-onset high myopia in five Chinese families

Novel mutations of the X-linked genes associated with early-onset high myopia in five Chinese families

Managing the apparently blind child presenting in the first year of life: A review

IMI—Management and Investigation of High Myopia in Infants and Young Children

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