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Human Genetics Jan 2023Oculocutaneous albinism (OCA) is a group of Mendelian disorders characterized by hypopigmentation of skin, hair and pigmented ocular structures. While much of the...
Oculocutaneous albinism (OCA) is a group of Mendelian disorders characterized by hypopigmentation of skin, hair and pigmented ocular structures. While much of the genetic heterogeneity of OCA has been resolved, many patients still lack a molecular diagnosis following exome sequencing. Here, we report a consanguineous family in which the index patient presented with OCA and Hirschsprung disease but tested negative for known genetic causes of OCA. Instead, he was found to have a homozygous presumptive loss of function variant in PMEL. PMEL encodes a scaffolding protein that is essential for the normal maturation of melanosomes and normal deposition of the melanin pigment therein. Numerous PMEL vertebrate ortholog mutants have been reported and all were characterized by conspicuous pigmentary abnormalities. We suggest that the patient we report is the first human equivalent of PMEL loss of function.
Topics: Male; Humans; Albinism, Oculocutaneous; Homozygote; Consanguinity; Mutation; gp100 Melanoma Antigen
PubMed: 36166100
DOI: 10.1007/s00439-022-02489-y -
Ophthalmic Genetics Dec 2022Albinism is a group of genetic disorders characterized by general skin and retinal hypopigmentation. It is in most cases an autosomal recessive condition. Foveal...
BACKGROUND
Albinism is a group of genetic disorders characterized by general skin and retinal hypopigmentation. It is in most cases an autosomal recessive condition. Foveal hypoplasia (FH) is one of the main criteria for the diagnosis of albinism. The aim of this study was to analyze the macular profile of the parents of patients with albinism.
METHODS
This study included a case series of 27 patients with albinism seen in Rothschild Foundation between April 2017 and February 2020. Spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCT-A) were performed in every patient when possible and in every available parents. FH was graded according to Thomas' classification based on OCT. Next generation sequencing-based gene panel testing was performed in parents and children when a FH was detected on OCT in a parent.
RESULTS
Twenty-seven patients with albinism were examined. Nine parents had FH based on the OCT B-scan (33%). In parents without FH based on the SD-OCT B-scan (67%), OCT-A showed a reduced avascular zone in the deep vascular plexus in 4 parents. Six parents carried variants that could explain their phenotype, including TYR R402Q hypomorphic alleles.
CONCLUSION
This study showed the presence of FH in parents of patients with albinism, and aimed to genetically explain this phenotype.
Topics: Humans; Fovea Centralis; Retina; Albinism; Albinism, Oculocutaneous; Albinism, Ocular; Vision Disorders; Tomography, Optical Coherence
PubMed: 36098180
DOI: 10.1080/13816810.2022.2121841 -
Frontiers in Genetics 2022Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is...
Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is predominantly caused by mutations in the gene. IIN poses a diagnostic challenge as underlying pre-symptomatic "multisystem" disorders varying from benign to life-threatening should first be ruled out before nystagmus can be labeled as idiopathic. A multidisciplinary approach including multimodal ocular investigations and next-generation sequencing with whole-genome sequencing (WGS) or targeted gene panel testing is required to delineate the exact etiology. We report the clinical and genetic outcomes of 22 patients, from 22 unrelated families of diverse ethnicities, with IIN seen in the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between 2016 and 2022. Thirty-six percent (8/22) received a confirmed molecular diagnosis with eight mutations identified in two genes (seven in including one novel variant c.706_707del; p. [Lys236Alafs*66], and one in ). This study expands the mutational spectrum of IIN and highlights the significant role of an integrated care pathway and broader panel testing in excluding underlying pathologies.
PubMed: 36072665
DOI: 10.3389/fgene.2022.977806 -
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 -
Journal of Optometry 2023To describe the prevalence and severity of photosensitivity in patients with albinism, and to compare with ocular features and how this correlated with use and choice of...
PURPOSE
To describe the prevalence and severity of photosensitivity in patients with albinism, and to compare with ocular features and how this correlated with use and choice of optical filters.
METHODS
Cross-sectional study on 81 participants with ocular or oculocutaneous albinism. An ophthalmic evaluation including visual acuity, contrast sensitivity and evaluation of iris translucency and fundus hypopigmentation was performed. Participants were offered optical rehabilitation with testing of a wide panel of filters. The associations between ocular characteristics, subjective photosensitivity complaints, and filter choice were evaluated.
RESULTS
Photosensitivity was rated as "some" to "worst imaginable" in 77.8% of participants. Severity of photosensitivity correlated significantly with fundus hypopigmentation (p = 0.04) but not with iris translucency (p = 0.14) and it was worse in those with poor visual acuity but there was no association between photosensitivity and contrast vision. Seventy-four new pairs of spectacles were prescribed in the study. All outdoor spectacles contained a filter, whereas 26.5% of new indoor spectacles did not. Relatively neutral filter colors (gray, brown or a combination of gray and brown with other colors) and low transmission were preferred.
DISCUSSION
Photosensitivity is common in albinism, but research targeting treatment is limited. Color and neutral filters with a low light transmission were preferred, with participants having a large number of spectacles, presumably to meet their needs in different situations.
Topics: Humans; Cross-Sectional Studies; Albinism; Albinism, Oculocutaneous; Vision, Ocular; Visual Acuity
PubMed: 36028395
DOI: 10.1016/j.optom.2022.07.002 -
European Journal of Medical Genetics Oct 2022Oculocutaneous albinism type 2 (OCA2) is a pigmentation disorder characterized by hypopigmentation of the skin, hair and eyes and ocular features. Sickle cell disease...
Oculocutaneous albinism type 2 (OCA2) is a pigmentation disorder characterized by hypopigmentation of the skin, hair and eyes and ocular features. Sickle cell disease (SCD) is caused either by homozygosity of the beta globin gene variant c.20A > T/p.Glu6Val giving rise to severe anemia or by combined abnormal hemoglobins (HbS/βthal) leading to mild SCD. We report a 45 years old female patient from the Democratic Republic of Congo affected with these two disorders. She presented with creamy white skin and numerous pigmented patches called dendritic freckles, nystagmus, foveal hypoplasia grade 2, photophobia and very poor visual acuity. Sequencing of the OCA2 gene identified the common exon 7 deletion and a new pathogenic variant c.1444A > C/p.Thr482Pro. She had mild SCD with a total Hb level of 101 g/l. Hbβ sequencing identified variants c.20A > T giving rise to HbS and c.315 + 1 G > A characteristic of β-thalassemia. A heterozygous 3.7 kb deletion of the α globin gene was also found. The combined Hbβ/α globin genotype explains the mild SCD phenotype. Co-occurrence of OCA2 and SCD raises the question whether the patient's phenotype simply results from the addition of the two diseases' phenotypes or whether interaction between the two diseases modulates the phenotype of each other.
Topics: Albinism, Oculocutaneous; Anemia, Sickle Cell; Carrier Proteins; Democratic Republic of the Congo; Female; Genotype; Humans; alpha-Globins
PubMed: 35964929
DOI: 10.1016/j.ejmg.2022.104594 -
Ophthalmic Surgery, Lasers & Imaging... Aug 2022This case series details macular findings in three female siblings who were found to be carriers of a previously unreported splice mutation in GPR143 (X-linked ocular...
This case series details macular findings in three female siblings who were found to be carriers of a previously unreported splice mutation in GPR143 (X-linked ocular albinism [OA1]). Presumed lyonization is responsible for both the subtle and varied findings in OA1 carriers, even among siblings, and especially in patients with darker skin pigmentation. In this series, we used green-light autofluorescence to reveal subtle subfoveal involvement and used optical coherence tomography angiography to uncover previously unreported narrowing of the foveal avascular zone, consistent with foveal hypoplasia. .
Topics: Albinism, Ocular; Eye Proteins; Female; Humans; Membrane Glycoproteins; Mutation
PubMed: 35951714
DOI: 10.3928/23258160-20220713-03 -
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 -
Genes Jul 2022Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive syndromic form of albinism, characterized by oculocutaneous albinism (OCA) and other systemic...
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive syndromic form of albinism, characterized by oculocutaneous albinism (OCA) and other systemic complications. The purpose of this study was to investigate patients with HPS-associated gene mutations and describe associated ocular and extraocular phenotypes. Fifty-four probands clinically diagnosed as albinism were enrolled. Ophthalmic examinations and genetic testing were performed in all subjects. The phenotypic and genetic features were evaluated. HPS-associated gene mutation was identified in four of the patients with albinism phenotype. Clinically, photophobia, and nystagmus was detected in all (4/4) patients, and strabismus was found in one (1/4) patient. Fundus examination revealed fundus hypopigmentation and foveal hypoplasia in all (8/8) eyes. Eight novel causative mutations were detected in these four HPS probands. Five (62.5%, 5/8) of the mutations were nonsense, two of the mutations were missense (25%, 2/8), and one of the mutations was frameshift (12.5%, 1/8). All patients in our study carried compound heterozygous variants, and all these pathogenic variants were identified to be novel, with most (62.5%, 5/8) of the mutations being nonsense. Our results improved the understanding of clinical ocular features, and expanded the spectrum of known variants and the genetic background of HPS.
Topics: Eye; Genetic Testing; Hermanski-Pudlak Syndrome; Humans; Mutation; Phenotype
PubMed: 35886065
DOI: 10.3390/genes13071283 -
Indian Journal of Ophthalmology Jul 2022To assess the clinical profiles, presenting ocular features, and variations in the phenotypic features in siblings with oculocutaneous albinism (OCA).
PURPOSE
To assess the clinical profiles, presenting ocular features, and variations in the phenotypic features in siblings with oculocutaneous albinism (OCA).
METHODS
Electronic medical records of consecutive siblings diagnosed with albinism from January 2016 to December 2020 were reviewed to identify the affected siblings. The variations in their phenotypic characteristics were studied.
RESULTS
Significant variations were observed in the clinical features between the siblings (n = 42). A difference of >2 lines in visual acuity was observed in 50% (n = 21) of the sibling pairs. Compound hyperopic astigmatism was the commonest refractive error. The refractive status was different in 80.95% (n = 34) pairs. Although individually strabismus and abnormal head posture were observed in one-third and one-fourth of individual children, respectively, both siblings with similar strabismus were seen in only 16.67% (n = 7) and with a similar abnormal head posture in 13.33% (n = 5). Nystagmus was the most consistent finding across these siblings with a similar nature of horizontal jerk or pendular in 65% of sibling pairs.
CONCLUSION
This study observed significant variations in phenotypic presentations among siblings with OCA. Such differences in clinical manifestations and severity would be helpful in appropriate counseling of these families as the need for rehabilitation services is likely to vary across siblings.
Topics: Albinism, Oculocutaneous; Biological Variation, Population; Child; Eye; Humans; Siblings; Strabismus
PubMed: 35791147
DOI: 10.4103/ijo.IJO_1025_22