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Graefe's Archive For Clinical and... Jul 2022Albinism defines a group of genetic diseases which result from disordered melanin biosynthesis. Proliferative diabetic retinopathy (PDR) results from poorly controlled... (Observational Study)
Observational Study
PURPOSE
Albinism defines a group of genetic diseases which result from disordered melanin biosynthesis. Proliferative diabetic retinopathy (PDR) results from poorly controlled type 1 or 2 diabetes mellitus (DM) and can lead to blindness due to progressive neovascularisation. However, the treatment of PDR in patients with ocular/oculocutaneous albinism may be more challenging. In this study, we compared a group of patients with albinism and PDR, to a group with albinism and diabetes mellitus but no PDR, to examine the long-term implications.
METHODS
Retrospective observational study included all patients with ocular albinism (OA) or oculocutaneous albinism (OCA) and DM who presented at a single specialist centre. Participants were allocated into either group 1 (eyes with PDR) or group 2 (all eyes without PDR). Statistical analysis was performed using SPSS V26.0. Between-group differences were investigated.
RESULTS
Outcome data was available for 5 eyes from 3 participants in group 1 and 26 eyes from 13 participants in group 2. Despite interventions, a large and significant difference in vision at follow-up was observed between group 1 and group 2 (mean change in visual acuity: 1.11 (± 1.00) versus - 0.15 (± 0.46), respectively; p = < 0.0001).
CONCLUSION
PDR is associated with poor long-term prognosis despite interventions for patients with albinism. Those without PDR appear to maintain stable vision. Alternative treatments for PDR and its complications may be required in this population. Measures to prevent the development of diabetic eye disease and progression towards PDR should be employed at an early stage.
Topics: Albinism; Albinism, Oculocutaneous; Diabetes Mellitus; Diabetic Retinopathy; Humans; Hyperopia; Neovascularization, Pathologic; Visual Acuity
PubMed: 35072785
DOI: 10.1007/s00417-021-05313-x -
BMC Medical Genomics Sep 2023To 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...
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.
Topics: Child; Child, Preschool; Humans; Male; Cytoskeletal Proteins; East Asian People; Genes, X-Linked; Membrane Proteins; Mutation; Myopia; Age of Onset; Exome Sequencing; Pedigree
PubMed: 37749571
DOI: 10.1186/s12920-023-01665-x -
Progress in Retinal and Eye Research Nov 2017The domestic chicken, Gallus gallus, serves as an excellent model for the study of a wide range of ocular diseases and conditions. The purpose of this manuscript is to... (Review)
Review
The domestic chicken, Gallus gallus, serves as an excellent model for the study of a wide range of ocular diseases and conditions. The purpose of this manuscript is to outline some anatomic, physiologic, and genetic features of this organism as a robust animal model for vision research, particularly for modeling human retinal disease. Advantages include a sequenced genome, a large eye, relative ease of handling and maintenance, and ready availability. Relevant similarities and differences to humans are highlighted for ocular structures as well as for general physiologic processes. Current research applications for various ocular diseases and conditions, including ocular imaging with spectral domain optical coherence tomography, are discussed. Several genetic and non-genetic ocular disease models are outlined, including for pathologic myopia, keratoconus, glaucoma, retinal detachment, retinal degeneration, ocular albinism, and ocular tumors. Finally, the use of stem cell technology to study the repair of damaged tissues in the chick eye is discussed. Overall, the chick model provides opportunities for high-throughput translational studies to more effectively prevent or treat blinding ocular diseases.
Topics: Animals; Biomedical Research; Chickens; Disease Models, Animal; Eye; Eye Diseases; Tomography, Optical Coherence; Vision Disorders
PubMed: 28668352
DOI: 10.1016/j.preteyeres.2017.06.004 -
American Journal of Medical Genetics.... Jul 2018Ocular albinism type 1 (OA1) is caused by mutations in the GPR143 gene located at Xp22.2. The manifestations, which are due to hypopigmentation, are confined to the eyes...
Ocular albinism type 1 (OA1) is caused by mutations in the GPR143 gene located at Xp22.2. The manifestations, which are due to hypopigmentation, are confined to the eyes and optic pathway. OA1 associated with late-onset sensorineural hearing loss was previously reported in a single family and hypothesized to be caused by a contiguous gene deletion syndrome involving GPR143 and the adjacent gene, TBL1X. Here, we report on a family with OA1, infertility, late-onset sensorineural hearing loss, and a small interstitial Xp microdeletion including the GPR143, TBL1X, and SHROOM2 genes. In addition, we re-examined a patient previously described with OA1, infertility and a similar Xp deletion with audiologic follow-up showing a late-onset sensorineural hearing loss. Our results raise an intriguing question about the possibility for TBL1X (absence) involvement in this type of hearing loss. However, our study cannot claim a causative relationship and more convincing evidence is needed before the hypothesis can be accepted that TBL1X could be involved in late-onset sensorineural hearing loss and that ocular albinism with late-onset sensorineural hearing loss can present itself as a contiguous gene deletion/microdeletion syndrome. The finding of infertility in all affected male patients demonstrates that this deletion, including the SHROOM2 gene, may be a potentially causative X-linked genetic factor of male infertility.
Topics: Adult; Aged; Albinism, Ocular; Eye Proteins; Female; Gene Deletion; Genetic Diseases, X-Linked; Hearing Loss, Sensorineural; Humans; Infertility; Male; Membrane Glycoproteins; Membrane Proteins; Middle Aged; Mutation; Pedigree; Transducin
PubMed: 30160833
DOI: 10.1002/ajmg.a.38836 -
Archivos de La Sociedad Espanola de... Feb 2023To identify the ocular pathologies that are reported as causes of low vision in children.
OBJECTIVE
To identify the ocular pathologies that are reported as causes of low vision in children.
MATERIAL AND METHODS
The systematic search was carried out in Medline (PubMed), Embase and Lilacs. Observational studies with populations between 0-18 years of age, reporting visual acuity data between 20/60-20/400 and reporting the frequency of ocular pathologies were selected. Studies in which the diagnosis of the condition had not been verified by a professional, or which covered only cases of blindness, uncorrected refractive errors, or amblyopia, were excluded. The methodological quality of the articles was evaluated using the Joanna Briggs Institute instrument for prevalence studies.
RESULTS
27 studies conducted in Asia (13 publications), Africa (6 studies), Oceania (4 studies), Europe and South America (2 studies each) were included. The most reported causes of low vision were: cataract, with prevalence between 0.8% and 27.2%; albinism with from 1.1% to 47%; nystagmus, with prevalence between 1.3% and 22%; retinal dystrophies between 3.5% and 50%; retinopathy of prematurity (ROP) with prevalence between 1.1% and 65.8%, optic atrophy between 0.2% and 17.6%, and glaucoma from 2.4% to 18.1%.
CONCLUSIONS
Cataract, albinism and nystagmus are the ocular pathologies most mentioned by studies as a cause of low vision in children, as well as retinal diseases such as ROP and optic nerve diseases such as atrophy. However, there are numerous eye conditions that can result in low vision in the pediatric population.
Topics: Infant, Newborn; Humans; Child; Vision, Low; Blindness; Glaucoma; Cataract; Retinopathy of Prematurity; Nystagmus, Pathologic
PubMed: 36068132
DOI: 10.1016/j.oftale.2022.06.016 -
Indian Journal of Ophthalmology Jul 2022To describe the distribution of ocular disorders in patients with a family history of consanguinity presenting to a multi-tier ophthalmology hospital network in India.
PURPOSE
To describe the distribution of ocular disorders in patients with a family history of consanguinity presenting to a multi-tier ophthalmology hospital network in India.
METHODS
This cross-sectional hospital-based study included 2,805,267 new patients presenting between August 2010 and April 2021. Patients with a family history of consanguinity were included as cases. The sociodemographic and clinical data were collected using an electronic medical record system.
RESULTS
Overall, 20,445 (0.73%) new patients were documented to have a family history of consanguinity. The prevalence rates were 4.04% in children (age: <16 years) and 0.21% in adults. The mean age of the patients was 11.87 ± 11.06 years. The majority of the patients were males (56.48%) and students (54.43%) by profession. The majority (93.05%) of the patients were in the 0-30-years age bracket, with over half of them (53.71%) presenting in the first decade of life. A significant number of patients were from higher socioeconomic status (73.48%) and the rural region (47.62%). The most common degree of consanguinity documented was second degree (3.95%). The most common ocular disorders associated with a high proportion of consanguinity were congenital hereditary endothelial dystrophy (CHED) (100%), corneal macular dystrophy (83.78%), xeroderma pigmentosum (80.95%), and ocular albinism (73.59%). A tenth of the patients (9.8%) reported a similar history of ocular disorders among the family members and more commonly among the siblings (70.4%).
CONCLUSION
Consanguineous marriages are not uncommon in India. They cause ocular disorders that cause visual impairment in a significant majority of those affected in their early decades of life. Genetic counseling plays a role in prevention.
Topics: Adolescent; Adult; Child; Child, Preschool; Consanguinity; Cross-Sectional Studies; Data Science; Electronic Health Records; Eye Diseases; Female; Humans; India; Infant; Male; Young Adult
PubMed: 35791120
DOI: 10.4103/ijo.IJO_1553_21 -
Frontiers in Pharmacology 2019l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective therapeutic agent for Parkinson's disease (PD). l-DOPA is traditionally believed to be an inert amino acid... (Review)
Review
l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective therapeutic agent for Parkinson's disease (PD). l-DOPA is traditionally believed to be an inert amino acid that exerts actions and effectiveness in PD through its conversion to dopamine. In contrast to this generally accepted idea, l-DOPA is proposed to be a neurotransmitter. Recently, GPR143 (OA1), the gene product of was identified as a receptor candidate for l-DOPA. GPR143 is widely expressed in the central and peripheral nervous system. GPR143 immunoreactivity was colocalized with phosphorylated α-synuclein in Lewy bodies in PD brains. GPR143 may contribute to the therapeutic effectiveness of l-DOPA and might be related to pathogenesis of PD.
PubMed: 31632270
DOI: 10.3389/fphar.2019.01119 -
Annales de Dermatologie Et de... Dec 2021Long-term and ongoing support in accordance with the changing needs of patients and their families is one of the main components of patient care, including therapeutic...
BACKGROUND
Long-term and ongoing support in accordance with the changing needs of patients and their families is one of the main components of patient care, including therapeutic patient education (TPE).
OBJECTIVE
To co-construct a TPE program for albinism with all those involved in the management of albinism patients.
METHODS
Eight steps have been defined for the co-construction process: 1) identify all the relevant experts and invite them to participate in the construction of a TPE program to improve care for and support of patients with albinism, 2) review and analyse all publications regarding TPE for albinism, 3) conduct semi-structured interviews with the patients' parents, 4) conduct brainstorming meetings with the participating experts for an exchange of experience and expertise, 5) elaborate the program's concrete content with the experts, 6) draw up a TPE skills checklist, 7) create TPE educational tools to facilitate learning, 8) review and summarize each step of the co-construction protocol.
RESULTS
Co-construction of a TPE program for children, adolescents, and young adults with albinism, and their parents.
CONCLUSION
Strengths and advantages of the co-construction process include: i) highlighting of the experiential knowledge mentioned in the repository, ii) multiplicity of points of view and perspectives, iii) rapid improvement in TPE training both for the association and the patients, iv) awareness of the shift caregivers' position with regards to TPE and recognition of the polysemy of their discourse. The TPE program for albinism has been authorized since 2018.
Topics: Adolescent; Albinism; Child; Humans; Parents; Patient Education as Topic
PubMed: 34217528
DOI: 10.1016/j.annder.2021.03.005 -
Genes Nov 2022Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations...
Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations in at least 20 different genes have been identified. Oculo-cutaneous Albinism type IV (OCA4) is the most frequent form in Asia but has been reported in all populations, including Europeans. Little is known about the genotype-phenotype correlation. We identified two main phenotypes via the analysis of 30 OCA4 patients with a molecularly proven diagnosis. The first, found in 20 patients, is clinically indistinguishable from the classical OCA1 phenotype. The genotype-to-phenotype correlation suggests that this phenotype is associated with homozygous or compound heterozygous nonsense or deletion variants with frameshift leading to translation interruption in the gene. The second phenotype, found in 10 patients, is characterized by very mild hypopigmentation of the hair (light brown or even dark hair) and skin that is similar to the general population. In this group, visual acuity is variable, but it can be subnormal, foveal hypoplasia can be low grade or even normal, and nystagmus may be lacking. These mild to moderate phenotypes are associated with at least one missense mutation in .
Topics: Humans; Piebaldism; Mutation; Mutation, Missense; Phenotype; Genotype
PubMed: 36553465
DOI: 10.3390/genes13122198 -
International Journal of Molecular... Jul 2022Oculocutaneous albinism is an autosomal recessive disorder characterized by the presence of typical ocular features, such as foveal hypoplasia, iris translucency,...
Oculocutaneous albinism is an autosomal recessive disorder characterized by the presence of typical ocular features, such as foveal hypoplasia, iris translucency, hypopigmented fundus oculi and reduced pigmentation of skin and hair. Albino patients can show significant clinical variability; some individuals can present with only mild depigmentation and subtle ocular changes. Here, we provide a retrospective review of the standardized clinical charts of patients firstly addressed for evaluation of foveal hypoplasia and slightly subnormal visual acuity, whose diagnosis of albinism was achieved only after extensive phenotypic and genotypic characterization. Our report corroborates the pathogenicity of the two common polymorphisms p.(Arg402Gln) and p.(Ser192Tyr) when both are located with a pathogenic variant and aims to expand the phenotypic spectrum of albinism in order to increase the detection rate of the albino phenotype. Our data also suggest that isolated foveal hypoplasia should be considered a clinical sign instead of a definitive diagnosis of an isolated clinical entity, and we recommend deep phenotypic and molecular characterization in such patients to achieve a proper diagnosis.
Topics: Albinism; Albinism, Oculocutaneous; Eye Diseases, Hereditary; Fovea Centralis; Humans; Nystagmus, Congenital; Vision Disorders; Visual Acuity
PubMed: 35887175
DOI: 10.3390/ijms23147825