RESUMO
BACKGROUND: Albinism is a heterogeneous condition in which patients present complete absence, reduction, or normal pigmentation in skin, hair and eyes in addition to ocular defects. One of the heterogeneous forms of albinism is observed in Hermansky-Pudlak syndrome (HPS) patients. HPS is characterized by albinism and hemorrhagic diathesis due to the absence of dense bodies in platelets. METHODS: In this report, we describe a case of a pair of Puerto Rican siblings with albinism that were clinically diagnosed with HPS during childhood. Since they did not harbor the founder changes in the HPS1 and HPS3 genes common in Puerto Ricans, as adults they wanted to know the type of albinism they had. We performed exome sequencing, validation by PCR, and cloning of PCR products followed by Sanger sequencing in the family members. RESULTS: We discovered no mutations that could explain an HPS diagnosis. Instead, we found the siblings were compound heterozygotes for 4 variants in the Tyrosinase gene: c.-301C>T, c.140G>A (rs61753180; p.G47D), c.575C>A (rs1042602; p.S192Y), and c.1205G>A (rs1126809; p.R402Q). Our results show that the correct diagnosis for the siblings is OCA1B. CONCLUSION: Our study shows the importance of molecular testing when diagnosing a rare genetic disorder, especially in populations were the disease prevalence is higher.
Assuntos
Albinismo Oculocutâneo , Síndrome de Hermanski-Pudlak , Monofenol Mono-Oxigenase , Humanos , Síndrome de Hermanski-Pudlak/genética , Síndrome de Hermanski-Pudlak/diagnóstico , Síndrome de Hermanski-Pudlak/patologia , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/diagnóstico , Monofenol Mono-Oxigenase/genética , Masculino , Feminino , Adulto , Linhagem , Testes Genéticos/métodos , Mutação , HeterozigotoRESUMO
BACKGROUND: Multiple studies have examined the prevalence of nonmelanoma skin cancers (NMSC) in patients with oculocutaneous albinism (OCA). However, to date, no studies have examined this data in Caribbean populations. METHODS: This study is a cross-sectional study of 106 patients with OCA who were seen at the Oculocutaneous Albinism Clinic in Port-au-Prince and Gros Morne, Haiti, between the dates of February 2017 and June 2018. RESULTS: In our population, 31/106 (29%) patients were found to have NMSC, 10/31 (32%) had BCC, 12/31 (39%) had SCC, and 9/31 (29%) had both types of NMSC. The most common age groups were 31-40 years, with the overall range of ages being 18-63 years. Also, 60/106 (57%) of the patients had actinic keratoses (AK). CONCLUSIONS: Our study provides new data examining the prevalence of NMSC within a population of patients with OCA in Haiti. Overall, it shows that patients with albinism develop NMSC at an earlier age compared with the rest of the population. Therefore, appropriate skin cancer screening and surveillance should be implemented within this high-risk population group.
Assuntos
Albinismo Oculocutâneo , Neoplasias Cutâneas , Adolescente , Adulto , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/epidemiologia , Estudos Transversais , Haiti/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Adulto JovemRESUMO
Background: Oculocutaneous albinism (OCA) is a Mendelian disorder characterized by hypopigmentation of the skin, hair, and eyes, hypoplastic fovea, and low vision, known to be caused by mutations in the Tyrosinase (TYR) gene. Among the known TYR variants, some reduce but do not completely eliminate tyrosinase activity, allowing residual production of melanin and resulting in a contradictory assignment as either pathogenic or benign, preventing a precise clinical diagnostic.Materials and Methods: In the present work, we performed Whole Exome Sequencing and subsequent Sanger sequencing in a young male clinically diagnosed with OCA.Results: Whole-exome sequencing analysis revealed the identification of two variants in trans in TYR. The first, corresponds to a known pathogenic variant G47D, while the second S192Y, was considered a polymorphism due to its relatively high frequency in the European population.Conclusion: The lack of other pathogenic variants in TYR, the reported reduced enzymatic activity (ca. 40% respect to wt) for S192Y, together with the structural in-silico analysis strongly suggest that both reported variants are jointly disease-causing and that S192Y should be considered as likely pathogenic, especially when it is found in trans with a null variant.
Assuntos
Albinismo Oculocutâneo/genética , Monofenol Mono-Oxigenase/genética , Mutação de Sentido Incorreto/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Albinismo Oculocutâneo/diagnóstico , Sequência de Aminoácidos , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Sequenciamento do ExomaRESUMO
UNLABELLED: Previous studies have suggested that the G47D mutation leads patients to develop Oculocutaneous albinism (OCA) type IA. This mutation has been described in the Canary Islands. Historically, there has been a migration from the Canary Islands to some regions of Puerto Rico. OBJECTIVE: To report on the ocular findings of two Puerto Rican patients with OCA IA due to the G47D Tyrosinase gene mutation. PATIENT AND FINDINGS: Two unrelated patients with OCA underwent a comprehensive eye examination and were referred for genetic analysis. Patients had almost total iris transillumination, clear lenses, foveal hypoplasia with transparent maculae, and albinotic mid peripheries. Both patients had nystagmus, and only one patient had strabismus. CONCLUSIONS: Patients with the G47D muta- tion leading to OCA IA have poor visual acuities and poorly pigmented phenotypic ophthalmic findings. Further studies comparing ocular findings in patients th several mutations leading to OCA IA are warranted. To our knowledge this is the first report on ocular findings in Puerto Rican patients with OCA type IA with the rare G47D mutation.
Assuntos
Albinismo Oculocutâneo/genética , Monofenol Mono-Oxigenase/genética , Mutação , Albinismo Oculocutâneo/diagnóstico , Criança , Pré-Escolar , Humanos , Masculino , Porto RicoRESUMO
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease that displays genetic heterogeneity; there are 9 known subtypes. HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency and resultant bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Patients with HPS, specifically those with the genotypes HPS-1, HPS-2, or HPS-4, are predisposed to interstitial lung disease. In addition, some patients with HPS develop granulomatous colitis. Optimal health care requires a thorough knowledge of the unique health risks and functional limitations associated with this syndrome.
Assuntos
Síndrome de Hermanski-Pudlak/terapia , Assistência de Longa Duração/métodos , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/epidemiologia , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/terapia , Criança , Aberrações Cromossômicas , Comportamento Cooperativo , Comparação Transcultural , Estudos Transversais , Análise Mutacional de DNA , Avaliação da Deficiência , Diagnóstico Precoce , Genes Recessivos , Genótipo , Síndrome de Hermanski-Pudlak/diagnóstico , Síndrome de Hermanski-Pudlak/epidemiologia , Síndrome de Hermanski-Pudlak/genética , Humanos , Comunicação Interdisciplinar , Fenótipo , Deficiência do Pool Plaquetário/diagnóstico , Deficiência do Pool Plaquetário/epidemiologia , Deficiência do Pool Plaquetário/genética , Deficiência do Pool Plaquetário/terapia , Porto RicoRESUMO
OBJETIVO: Avaliar os métodos laboratoriais dos diferentes tipos de albinismo oculocutâneo (OCA 1 e OCA 2) de forma descritiva e analisar sua eficiência. MATERIAL E MÉTODO: O teste do bulbo capilar é um método químico usado para distinguir as duas formas, no entanto recentemente teve sua eficácia como teste padrão contestada. O avanço da biologia molecular permite a análise das mutações que causam o distúrbio e a sua localização gênica. CONCLUSÃO: O teste do bulbo é seguro apenas para o diagnóstico do OCA 1A, podendo ser usado como complemento de um método mais apurado. A análise molecular fornece um diagnóstico definitivo, permitindo distinguir OCA 1 de OCA 2, pois as mutações afetam genes em cromossomos diferentes.
OBJECTIVES: To evaluate the laboratories methods of the oculocutaneous albinism (OCA 1and OCA 2) of descriptive form and to analyze its results. METHODS: The hair bulb test is a chemical method used to distinguish the two forms, however, recently had its effectiveness as an standard test contested. The advance of molecular biology allows the analysis of the mutations that cause the disturb and its genic location. CONCLUSIONS: The bulb test is secure only for the diagnosis of OCA 1A, being able to be used as complement of a more refined method. The molecular analysis supplies a diagnostic definitive allowing to distinguish OCA 1 from OCA 2, because the mutations affect genes in different chromosomes.
Assuntos
Humanos , Albinismo Oculocutâneo/classificação , Albinismo Oculocutâneo/diagnóstico , Biologia Molecular/métodos , Técnicas de Laboratório ClínicoRESUMO
Objetivo. Describir el caso de una adolescente femenina de 18 años de edad, la cual presentaba dos genodermatosis: albinismo oculocutáneo e ictiosis vulgar. Caso clínico. La paciente mostró retardo en el desarrollo neurológico durante su infancia. No se encontraron antecendentes de padecimiento similar en otros miembros de la familia. El diagnóstico de albinismo e ictiosis fue confirmado por el estudio de fondo de ojo y el histopatológico. El iris de la paciente era translúcido y presentaba hipopigmentación de fondo de ojo; histopatológicamente con hiperqueratosis moderada sin paraqueratosis, con formación de grandes tapones queratósicos, sin presencia de acantosis. Conclusión. El presente caso corresponde clínica e histopatológicamente a albinismo oculotáneo con ictiosis vulgar, sin antecedentes de padecimiento similar en otros miembros de la familia
Assuntos
Humanos , Feminino , Adolescente , Albinismo Oculocutâneo/complicações , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/fisiopatologia , Albinismo/complicações , Albinismo/diagnóstico , Albinismo/fisiopatologia , Ictiose/complicações , Ictiose/diagnóstico , Ictiose/fisiopatologiaRESUMO
Hermansky-Pudlak syndrome (HPS) consists of ocu-locutaneous albinism, a platelet storage-pool deficiency, and ceroid lipofuscinosis. In a recent report on the cloning of an HPS gene, all 22 Puerto Rican HPS patients were homozygous for a 16-bp duplication in exon 15. This presumably reflected a founder effect for the HPS mutation in Puerto Rico. Nevertheless, we ascertained two individuals from central Puerto Rico who lacked the 16-bp duplication, exhibited significant amounts of normal-size HPS mRNA by northern blot analysis, and had haplotypes in the HPS region that were different from the haplotype of every 16-bp-duplication patient. Moreover, these two individuals displayed no mutations in their cDNA sequences, throughout the entire HPS gene. Both patients exhibited pigment dilution, impaired visual acuity, nystagmus, a bleeding diathesis, and absent platelet dense bodies, confirming the diagnosis of HPS. These findings indicate that analysis of Puerto Rican patients for the 16-bp duplication in HPS cannot exclude the diagnosis of HPS. In addition, HPS most likely displays locus heterogeneity, consistent with the existence of several mouse strains manifesting both pigment dilution and a platelet storage-pool deficiency.
Assuntos
Albinismo Oculocutâneo/genética , Heterogeneidade Genética , Albinismo Oculocutâneo/diagnóstico , Alelos , Plaquetas/ultraestrutura , Northern Blotting , Pré-Escolar , Análise Mutacional de DNA , Primers do DNA , Eletroforese em Gel de Ágar , Feminino , Haplótipos/genética , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Pigmentação/genética , Deficiência do Pool Plaquetário/diagnóstico , Deficiência do Pool Plaquetário/genética , Reação em Cadeia da Polimerase , Porto Rico , Sequências Repetitivas de Ácido Nucleico/genéticaRESUMO
The Hermansky-Pudlak syndrome (HPS) associates oculocutaneous albinism with a haemorrhagic diathesis and the accumulation of ceroid-like material in different tissues. HPS is not an uncommon type of albinism as it was diagnosed in 13.5% (8/59) of our autosomal recessive albinos. These eight patients were evaluated ophthalmologically and haematologically. Apart from the symptoms caused by the albinism, accompanying signs vary from ecchymoses to life threatening haemorrhages and death by associated restrictive lung disease. Recognition of this syndrome by the ophthalmologist can be of major importance in this serious and eventually fatal disorder.