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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ocular albinism type 1 (OA1) is an X-linked recessive disorder characterized by a major impairment of visual acuity, nystagmus, strabismus, photophobia and retinal hypopigmentation. From the analysis of patients carrying deletions and translocations involving the distal short arm of the X chromosome (Xp22.3) we have identified a region of approximately 110 kb in which the OA1 gene must lie. We have extensively searched for genes in this region using a variety of techniques which included exon amplification, cDNA selection and direct hybridization of cosmid inserts to cDNA libraries. Putative exons identified by exon amplification were used to screen a human retina cDNA library and several cDNA clones corresponding to an approximately 7.5 kb transcript were isolated and characterized. Transcripts of this newly identified gene were found to be abundant in retina and melanoma and could also be detected in brain, placenta, lung, kidney and pancreas. Interestingly, sequence analysis revealed that this new gene encodes a 1616 amino acid protein sharing significant similarities with the Apical Protein from Xenopus laevis (APX) which is implicated in amiloride-sensitive sodium channel activity. The gene, termed APXL (APX-Like), spans approximately 160 kb, contains 10 exons and covers over 70% of the 110 kb critical region for OA1. A truncated pseudogene sharing very high levels of homology with the rat eIF-5 gene, a eukaryotic translation initiation factor, was found to lie in the middle of intron 1. APXL was found deleted in two patients with contiguous gene syndromes including OA1 and in one patient with isolated OA1. Mapping, expression and patient analysis data led us to consider the APXL gene a strong candidate for the OA1 gene. DNA from 57 unrelated patients with OA1 was, therefore, scanned for mutations in the coding region, using both SSCP analysis and direct sequencing. No functionally significant mutation was identified, suggesting that APXL is not directly involved in OA1. Further studies are needed to clarify the physiologic role of this highly conserved gene.
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PMID:Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region. 779 90

Ocular albinism type 1 (OA1) is an inherited disorder characterized by severe reduction of visual acuity, photophobia, and retinal hypopigmentation. Ultrastructural examination of skin melanocytes and of the retinal pigment epithelium reveals the presence of macromelanosomes, suggesting a defect in melanosome biogenesis. The gene responsible for OA1 is exclusively expressed in pigment cells and encodes a predicted protein of 404 aa displaying several putative transmembrane domains and sharing no similarities with previously identified molecules. Using polyclonal antibodies we have identified the endogenous OA1 protein in retinal pigment epithelial cells, in normal human melanocytes and in various melanoma cell lines. Two forms of the OA1 protein were identified by Western analysis, a 60-kDa glycoprotein and a doublet of 48 and 45 kDa probably corresponding to unglycosylated precursor polypeptides. Upon subcellular fractionation and phase separation with the nonionic detergent Triton X-114, the OA1 protein segregated into the melanosome-rich fraction and behaved as an authentic integral membrane protein. Immunofluorescence and immunogold analyses on normal human melanocytes confirmed the melanosomal membrane localization of the endogenous OA1 protein, consistent with its possible involvement in melanosome biogenesis. The identification of a novel melanosomal membrane protein involved in a human disease will provide insights into the mechanisms that control the cell-specific pathways of subcellular morphogenesis.
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PMID:The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes. 879 53

A variety of paraneoplastic syndromes affect the central nervous system including eye. So far, two types of retinopathy are known to be associated with patients with malignancies, cancer-associated retinopathy (CAR), and melanoma-associated retinopathy (MAR). CAR is associated with epithelial cancers, mostly lung small cell carcinoma, and is characterized by retinitis pigmentosa-like retinal degeneration. Usually CAR can be found before an underlying primary cancer is diagnosed. MAR is associated with cutaneous malignant melanoma and is characterized by the relatively sudden onset of photophobia and nyctalopsia. The flash electroretinogram (ERG) of MAR patients shows a negative waveform, reduced b-wave amplitude, and reservation of a-wave amplitude, suggesting that bipolar cells may be affected. CAR and MAR are believed to result from an autoimmune response. In CAR, a calcium binding protein called recoverin, a 70 kDa protein, and neurofilaments are the retinal antigens recognized by the patient's serum. In contrast, the retinal antigens in MAR have not yet been identified, although patient sera specifically recognized retinal bipolar cells in immunocytochemistry.
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PMID:[Cancer-associated retinopathy]. 913 65

Oculocutaneous albinism is a rare autosomal recessive disorder characterized by general depigmentation, nystagmus, photophobia, and decreased visual acuity. Malignant melanoma is extremely rare in patients with albinism. We present a 41-year-old albino male patient, who was admitted with a suspected bronchogenic carcinoma. He underwent a pulmonary resection and the diagnosis was primary malign melanoma of the lung. The patient died of tumor recurrence in the postoperative 46th month.
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PMID:Primary malignant melanoma of the lung in oculocutaneous albino patient. 1157 44

Xeroderma pigmentosum (XP) was first described in 1874 by Hebra and Kaposi. [1] It is a rare autosomal recessive disorder characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development due to cellular hypersensitivity to ultraviolet radiation resulting from a defect in DNA repair. The basic defect in XP is in nucleotide excision repair (NER), leading to deficient repair of damaged DNA. A 12-year-old boy presented with a large growth over the right side of the forehead. The lesion was first noticed before two years as a 2 x 2 cm 2 mass. It was slowly growing and attained the present size of 10 x 8 x 7 cm 3 . The surface showed ulceration with areas of hemorrhage and blackish pigmentation. Also, the patient had hyperpigmented macules over the skin since early childhood. The macules appeared initially over the face and later developed over the other areas of the body. The macules were more over the sun exposed areas. He also had photophobia and both eyes showed corneal opacities. Histopathological examination of the excised growth showed features consistent with melanoma. This case is being presented because of its rare association with xeroderma pigmentosum patients in India.
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PMID:A case of melanoma in xeroderma pigmentosum. 1980 62

Multiple oculo-cutaneous malignancies are a common manifestation on sun-exposed facial areas in patients with Xeroderma pigmentosum (XP). Commonly seen are the basal cell carcinoma and the squamous cell carcinomas which manifest in the early first decade in contrast to fifth and sixth decade in the general population. XP manifests as photosensitivity, hyperpigmentation, premature skin aging and malignant changes like squamous cell carcinoma, basal cell carcinoma, fibrosarcoma and rarely malignant melanoma as well as internal malignancies. We report 11 cases of Xeroderma pigmentosa managed in our institute which included sex males and five females. All had photosensitivity, hyperpigmentation and consanguinity with facial malignant lesions like SCC and BCC. Ocular signs of photophobia and excessive lacrimation was seen in all the cases while blurring of vision due to corneal clouding, corneal injection, pterygium and limbal SCC were seen in 5 cases. SCC of the lids were seen in 7 cases while BCC seen in 8 cases and limbal and conjunctival SCC seen in one case. All were managed with excision while one case of melanoma with neck secondaries needed radical neck dissection while the other orbital exenteration. Oculo-cutaneous malignancies occur in the sun exposed areas so patients are advised regular follow up with speciality care. Awareness about the rare condition and importance of early detection and prevention of UV rays induced skin damage should be propagated. The disease is ultimately fatal, life can be prolonged by simple preventive measures to minimize sun exposure and early detection of the skin lesions and management.
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PMID:Xeroderma pigmentosum: clinicopathological review of the multiple oculocutaneous malignancies and complications. 2511 64

Oculocutaneous albinism (OCA), which is roughly divided into non-syndromic and syndromic OCA, is a group of autosomal recessive disorders caused by mutations in genes associated with pigmentation. Patients with OCA have hypopigmentation and ocular manifestations such as photophobia, amblyopia, and nystagmus. Hermansky-Pudlak syndrome (HPS), the most common syndromic OCA, is characterized by the additional features of a bleeding tendency and other critical systemic comorbidities such as pulmonary fibrosis and immunodeficiency. NGS-based gene analyses have identified several new causative genes for OCA and have detected rare subtypes of OCA with high accuracy including Japanese patients. In our survey of 190 Japanese OCA patients/families, OCA4 is the most common subtype (25.3%) followed by OCA1 (20.0%), HPS1 (14.7%), and OCA2 (8.4%). Similar to the A481T variant in OCA2, which is associated with a mild form of OCA2 and skin color variation, the c.-492_489delAATG variant located in the promoter region of SLC45A2 has been uniquely identified in Japanese patients with a mild form of OCA4. Further, rare OCA subtypes, including OCA3, HPS2, HPS3, HPS4, HPS5, HPS6, and HPS9, have also been identified in Japanese patients. The clinical characteristics and underlying molecular mechanisms of each subtype of OCA are concisely summarized in this review.
Pigment Cell Melanoma Res 2020 Sep 24
PMID:Current landscape of Oculocutaneous Albinism in Japan. 3296 95