Materiały źródłowe

• #1

  https://omim.org/entry/113750

  A number sign (#) is used with this entry because of evidence that oculocutaneous albinism-6 (OCA6) is caused by homozygous or compound heterozygous mutation in the SLC24A5 gene (609802) on chromosome 15q21. […] Oculocutaneous albinism (OCA) is a heterogeneous autosomal recessive disorder, with a worldwide prevalence of approximately 1:17,000. It manifests as a reduction or complete loss of melanin in the skin, hair, and eyes, often accompanied by eye symptoms such as photophobia, strabismus, moderate to severe visual impairment, and nystagmus (summary by Wei et al., 2013). […] The transmission pattern of OCA6 in the family reported by Wei et al. (2013) was consistent with autosomal recessive inheritance.

• #2 Albinism – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/albinism/

  People with non-syndromic OCA, a type of albinism, generally live as long as the average person. However, they do face a higher risk of getting skin cancer. The prognosis for albinism can also be affected by factors such as access to healthcare facilities, late diagnosis and treatment, and social stigma and discrimination. […] Albinism can increase the risk of skin cancers such as basal and squamous cell carcinomas (BCC, SCC). Among albinos, SCC is the most common, making up over 75% of cancer cases, with some diagnoses happening as early as the teenage years. Albinism can increase the risk of SCC by as much as 1000 times, particularly in the African population. […] Despite these challenges, it’s important to note that people with albinism have the same intelligence level as the general population. They may experience some delay in vision development, which could affect their education if not addressed early. Besides, issues related to self-perception and social exclusion can lead to feelings of loneliness and depression. Also, they seem to have a higher rate of attention deficit disorder.

• #3 Albinism: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001479.htm

  Albinism does not usually affect lifespan. However, the HPS form of albinism can shorten a person’s lifespan due to lung disease or bleeding problems. […] People with albinism may be limited in their outdoor activities because they can’t tolerate the sun.

• #4 Albinism: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1200472-overview

  Patients with albinism have a normal lifespan but there is an increased risk for skin cancer, and preventive measures are recommended for UV exposure. […] Genetic counseling is recommended for patients with albinism.

• #5 Oculocutaneous Albinism: What It Is, Symptoms & Prognosis

  https://my.clevelandclinic.org/health/diseases/oculocutaneous-albinism

  Oculocutaneous albinism is a lifelong disorder that can have a wide range of effects. Most people with OCA will have visible differences in their eyes, hair and/or skin. But those differences can vary. Some people will have differences that stand out, but not everyone with oculocutaneous albinism does. […] Most people with OCA will have various related health concerns, especially eye issues, but its rare for oculocutaneous albinism to cause dangerous or life-threatening issues on its own. The most important complication to avoid is skin damage from the sun or other sources of UV rays. […] With regular medical and vision care, most people with oculocutaneous albinism can expect a life like those who dont have OCA. This disorder usually doesnt affect your life expectancy, especially if you avoid skin cancer-related complications.

• #6 Albinism: Types, Symptoms, and Causes

  https://patient.info/skin-conditions/albinism-leaflet

  What is the outlook (prognosis)? Life expectancy is normal for a person with albinism. Although vision is usually severely impaired, intellect and development are normal. […] People with albinism have an increased risk of sunburn and of skin cancers as their skin is not protected by pigment.

• #7 Albinism: Types, Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/21747-albinism

  Albinism is a lifelong condition, but its manageable and typically doesnt affect a persons lifespan. […] If you have a genetic syndrome, your outlook depends on the other medical conditions you have and how they affect your body. Your healthcare provider can tell you more about what to expect in your unique situation.

• #8

  https://omim.org/entry/203200

  Throughout sub-Saharan Africa, OCA2 is responsible for a great deal of morbidity, with skin cancer and gross visual impairment being important sequelae. […] The estimated prevalence of OCA2 in Navajos is between 1:1,500 and 1:2,000. They estimated that this mutation originated from a single founder 400 to 1,000 years ago.

• #9

  https://omim.org/entry/203200

  A number sign (#) is used with this entry because oculocutaneous albinism type II (OCA2) is caused by homozygous or compound heterozygous mutation in the OCA2 gene (611409) on chromosome 15q. […] Tyrosinase-positive oculocutaneous albinism (OCA, type II; OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Although affected infants may appear at birth to have OCA type I, or complete absence of melanin pigment, most patients with OCA type II acquire small amounts of pigment with age. Individuals with OCA type II have the characteristic visual anomalies associated with albinism, including decreased acuity and nystagmus, which are usually less severe than in OCA type I (Lee et al., 1994; King et al., 2001). […] The transmission pattern of OCA2 in the families reported by Durham-Pierre et al. (1994) was consistent with autosomal recessive inheritance.

• #10 Evident hypopigmentation without other ocular deficits in Dutch patients with oculocutaneous albinism type 4 | Scientific Reports

  https://www.nature.com/articles/s41598-021-90896-y

  To describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4), we collected data on pigmentation (skin, hair, and eyes), visual acuity (VA), nystagmus, foveal hypoplasia, chiasmal misrouting, and molecular analyses of nine Dutch OCA4 patients from the Bartimus Diagnostic Center for complex visual disorders. […] OCA4 patients of this Dutch cohort all had hypopigmentation of skin, hair, and iris translucency. However, patients were either severely affected with regard to visual acuity, foveal hypoplasia, and misrouting, or visually not affected at all. […] We describe for the first time OCA4 patients with an evident lack of pigmentation, but normal visual acuity, normal foveal development and absence of misrouting. This implies that absence of melanin does not invariably lead to foveal hypoplasia and abnormal routing of the visual pathways.

• #11 Evident hypopigmentation without other ocular deficits in Dutch patients with oculocutaneous albinism type 4 | Scientific Reports

  https://www.nature.com/articles/s41598-021-90896-y

  Even though visual function was not affected in P1, P2, and P3, sufficient diagnostic criteria for albinism proposed by Kruijt et al. were met, i.e. a molecular diagnosis, combined with a major criterion (iris translucency) and at least two minor criteria (hypopigmentation of skin, hair, and fundus (all minor criteria)). […] The three OCA4 patients with normal visual development we describe in this report, are further proof that the relationship between pigmentation defect and ocular deficits in albinism is more complicated than previously thought. Further research is needed to unravel the mechanisms that cause some OCA4 patients to have a severe albinism phenotype, while others do not show any ocular deficit, apart from iris translucency.

• #12 Diagnostic Yield of Genetic Testing for Ocular and Oculocutaneous Albinism in a Diverse United States Pediatric Population

  https://www.mdpi.com/2073-4425/14/1/135

  The diagnostic yield of genetic testing for ocular/oculocutaneous albinism (OA/OCA) in a diverse pediatric population in the United States (U.S.) is unclear. […] Overall initial genetic diagnostic yield of OA/OCA was 66%. […] However, the diagnostic yield of OA (33%) was significantly lower (p = 0.007) than OCA (76%). […] There is a high diagnostic yield of genetic testing of patients overall with OA/OCA in a diverse U.S. based pediatric population. […] Presence or absence of cutaneous involvement of albinism significantly affects genetic diagnostic yield. […] A positive diagnostic yield of 70% in this U.S.-based population of patients with OCA and OA, after consideration of variant reclassification, falls within the range from prior studies in other countries with rates ranging from 28% to 91%.

• #13 Diagnostic Yield of Genetic Testing for Ocular and Oculocutaneous Albinism in a Diverse United States Pediatric Population

  https://www.mdpi.com/2073-4425/14/1/135

  Importantly, cutaneous involvement was a strong indicator for positive diagnostic yield and is likely related to the prevalence of the most common genes associated with OCA, TYR and OCA2. […] This study affirms the utility of genetic testing to guide the management of patients and families with OA and OCA.

• #14 Clinical evaluation and molecular screening of a large consecutive series of albino patients | Journal of Human Genetics

  https://www.nature.com/articles/jhg2016123

  As a result of this molecular study we estimated the frequencies of the different molecular forms in our cohort of 321 consecutive albino patients. We identified causative mutations accounting for: 44%, TYR; 17%, OCA2; 1%, TYRP1; 7%, SLC45A2; and 0.5%, SLC24A5. Male patients with a OA1 phenotype and GPR143 defects account for 5% of all cases. In 19% of OCA patients, a second reliable mutation (see Discussion below) was not detected, whereas 7% of our cases did not show any genetic alterations in the tested genes. […] Diagnosis of oculocutaneous albinism is principally based on clinical examination and may be classified according to the hypopigmentation trait (relative to other family members) and to the ophthalmic findings. […] It is still unclear why the same type of mutations leads to different degrees of ocular disorders. This variability may reflect the effect of modifier genes and/or environmental factors leading to incomplete penetrance and variable expression of OCA alleles. Characterization of such modifier genes will be essential for improving OCA phenotype prediction.

• #15 Clinical evaluation and molecular screening of a large consecutive series of albino patients | Journal of Human Genetics

  https://www.nature.com/articles/jhg2016123

  Unresolved cases and apparently digenic OCA inheritance could be explained by the presence of genetic alterations located in the promoter, in noncoding genomic regions or far away from the locus in relevant transcriptional regulators sequence, or by the presence of exonic unrecognized splicing mutations, large deletions or complex gene rearrangements not detectable by Sanger sequencing. Therefore, in the near future, we consider a next-generation sequencing approach essential for molecular diagnosis of albino patients, including entire OCA/OA genes (exons, introns and flanking regions) in order to identify rearrangements embedded in the introns or in the regulatory regions or gene dosage anomalies with reading depth measurements. The existence of new OCA loci yet to be identified could obviously be considered.

• #16 Abnormal foveal morphology in carriers of oculocutaneous albinism | British Journal of Ophthalmology

  https://bjo.bmj.com/content/107/8/1202

  Foveal hypoplasia was identified in 32.14% of OCA carriers; grade 1 in all cases. […] We have, for the first time, identified foveal abnormalities in OCA carriers. This provides clinical value, particularly in cases where limited phenotype data are available. Our findings raise the possibility that previously reported mild cases of foveal hypoplasia or isolated foveal hypoplasia could correspond to OCA carrier status. […] Our findings may improve phenotyping in OCA and provide clinical value, particularly in cases where limited phenotype or genotype data are available. […] We have described for the first time, foveal abnormalities associated with carriers of autosomal recessive OCA. We identified that approximately a third of our OCA carrier study population (32.1%) had foveal hypoplasia.

• #17 Abnormal foveal morphology in carriers of oculocutaneous albinism | British Journal of Ophthalmology

  https://bjo.bmj.com/content/107/8/1202

  Our findings suggest there is an element of arrested retinal development that occurs in OCA carriers, indicative of reduced TYR activity despite only carrying one mutant allele. […] Despite the presence of foveal hypoplasia, we only found minimal visual consequence in OCA carriers. […] Our observation of low grades of foveal hypoplasia associated with carriers of OCA may provide one potential explanation for some milder cases of albinism.

• #18 Clinical evaluation and molecular screening of a large consecutive series of albino patients | Journal of Human Genetics

  https://www.nature.com/articles/jhg2016123

  Oculocutaneous albinism (OCA) is characterized by hypopigmentation of the skin, hair and eye, and by ophthalmologic abnormalities caused by a deficiency in melanin biosynthesis. […] This comprehensive study of a consecutive series of OCA/OA1 patients allowed us to perform a clinical evaluation of the different OCA forms. […] In OCA patients hypopigmentation of the skin causes severe photosensitivity and an increase risk of developing sun-induced skin cancer. This implies the need for albino patients of accurate dermatological controls during the lifetime. […] In this study we analyzed a consecutive series of 321 albino patients reporting genetic frequencies of the main causative genes and 70 novel mutations. This comprehensive work allowed us to perform clinical evaluation of our albino patients and to estimate the relative frequencies of the different molecular forms in our population.

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