1,721,043 research outputs found
Use of next generation sequencing for isolated and syndromic Anophthalmia, Microphthalmia and Coloboma (MAC): a new approach to molecular genetic diagnosis
Full text linkABSTRACT: Use of Next Generation Sequencing for isolated and syndromic Anophthalmia, Microphthalmia and Coloboma (MAC): a new approach to molecular genetic diagnosis
Department in Cellular Biotechnologies and Hematology
PhD in Human Biology and Medical Genetics
Supervisor: Prof. Pizzuti Antonio
Correlator: Prof. Novelli Antonio
Phd student: Dott. Iapichino Giuseppe
In these last few years, both mendelian and complex diseases have reached a higher level of accuracy in the analytical process, with a more efficient diagnostic definition and also a more detailed genotype-phenotype correlation. Complex syndromic pathologies, such as microphthalmia and anophthalmia, often accompanied by complex clinical pictures, and characterized by a high level of genetic and phenotypic heterogeneity, can now be handled in a faster and thorough manner. Currently, national or international shared guidelines have yet to be defined and a phenotypic or genetic classification of these diseases is still missing. Similarly to what happens for most rare diseases, the diagnostic and care management of children with ocular syndromes suffers heavily from the absence of strong scientific knowledge that would help in the development of shared guidelines, mainly because the phenotypic heterogeneity of these diseases is massive. The aim of this project was to carefully investigate the genes involved in microphthalmia, anophthalmia, coloboma and related syndromic diseases using Next Generation Sequencing. This new molecular approach allows to make a massive sequencing of different genomic regions. The possibility to analyze millions of sequencing reactions in parallel at very reduced costs, with shorter processing times and very little amounts of initial DNA, has provided a formidable boost for the study of rare diseases. In the present study, a panel of different genes involved in the ocular development has been designed to simultaneously and rapidly analyze multiple ocular genes of a patient by using the Illumina-Nextseq 500 platform. NGS allowed us to analyze several genes for a given patient and to identify variants both in genes directly involved in the pathogenesis of anophthalmia, microphthalmia and coloboma, both in genes not directly implicated in syndromic or isolated MACs. This allowed us to understand at a molecular level many of those phenotypes described as shaded, atypical or not perfectly defined in a specific syndrome. In this regard, the continuous interaction with the referring physicians has been fundamental in our study, highlighting the importance of the collaboration between the lab scientist and the clinical geneticist that will eventually help to find a link between the phenotypes described and the many variants still to be identified
Carbamazepine-induced eruption histologically mimicking mycosis fungoides
No full textCarbamazepine is an important drug used in the management of seizures, trigeminal neuralgia, and chronic pain syndromes. It has been associated with a variety of adverse skin reactions including urticaria, lichenoid eruptions, erythroderma, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A 39-year-old white male had been started on carbamazepine for intractable pain which resulted from a right foot crush injury. Approximately 3 months after the start of therapy, the patient had developed a generalized skin eruption following an entire day of sun exposure. Skin biopsies revealed an atypical lymphoid infiltrate in the dermis with collections of the atypical lymphocytes within spongiotic vesicles in the epidermis, suggestive of mycosis fungoides. The patient was treated with systemic prednisone. Subsequent biopsies failed to reveal atypical lymphocytes. Previous reports have described spongiotic eruptions with foci of atypical lymphocytes in contact dermatitis and in patients treated with phenytoin. To the best of our knowledge, this is the first reported case of a carbamazepine-induced eruption simulating mycosis fungoides histologically
LICHENOID DRUG ERUPTION SECONDARY TO PROPRANOLOL
No full textPropranolol, a widely prescribed beta-adrenergic receptor blocker, has occasionally been associated with adverse cutaneous reactions. We present a case of ulcerative lichenoid drug eruption of the penis secondary to propranolol therapy. This unusual clinical presentation has not been described previously in the literature
Unusual presentation of cutaneous metastatic malignant melanoma
No full textThis report describes an unusual presentation of cutaneous metastases suspected to have occurred through lymphatic spread in a patient with malignant melanoma. Punctate papular skin lesions correlated histologically with small tumor foci in the papillary dermis
Superficial granulomatous pyoderma
No full textSuperficial granulomatous pyoderma, recently described as a variant of pyoderma gangrenosum, would be better termed pathergic granulomatous cutaneous ulceration as the seven previously described cases, as well as our own two cases, have significant dermal involvement histologically and heal with scarring. In contrast to pyoderma gangrenosum, lesions of superficial granulomatous pyoderma respond to less toxic anti-inflammatory agents
Asymptomatic esophageal squamous cell carcinoma masquerading as a rare primary pancreatic carcinoma. Diagnosis by percutaneous fine needle aspiration
No full textAn unusual case of asymptomatic squamous cell carcinoma of the esophagus metastatic to the pancreas, mimicking a rare primary pancreatic neoplasm, is reported. Percutaneous fine needle aspiration (FNA) biopsy of a pancreatic lesion showed squamous cell carcinoma, which in the pancreas is virtually always metastatic in origin. This prompted a search for an occult primary elsewhere, resulting in the discovery of an esophageal neoplasm, which in itself is one of the least likely sources of pancreatic metastases. FNA biopsy was thus a useful and accurate diagnostic tool in establishing the true nature of the pancreatic neoplasm, sparing the patient unnecessary pancreatic surgery, with its attendant morbidity and hospital costs
PEUTZ-JEGHERS-LIKE MELANOTIC MACULES ASSOCIATED WITH ESOPHAGEAL ADENOCARCINOMA
No full textA 67-year-old white man with esophageal adenocarcinoma presented with Peutz-Jeghers-like macules on the lips, face, nipples, and rectal mucosa. Pathological examination of the macules showed atypical melanocytes in the epidermis. The pleomorphic large melanocytes resembled the neoplastic cells seen in melanoma in situ. This is the first report of proliferation of atypical melanocytes in Peutz-Jeghers-like melanosis associated with a primary esophageal adenocarcinoma
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