ABSTRACT
OBJECTIVE: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide. METHODS: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 +/- 4.8 years) by clinical, neuropsychological, and molecular methodologies. RESULTS: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction. CONCLUSIONS: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature.
Subject(s)
Alzheimer Disease/genetics , Leucine/genetics , Methionine/genetics , Mutation/genetics , Presenilin-1/genetics , Adult , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/history , Brain/diagnostic imaging , Brain/pathology , Cognition Disorders/etiology , Cognition Disorders/genetics , Family Health , Female , Fluorodeoxyglucose F18 , Gene Frequency , Genetic Predisposition to Disease , Genetic Testing , Genotype , Global Health , History, 17th Century , History, 21st Century , Humans , International Cooperation , Italy , Male , Memory Disorders/etiology , Memory Disorders/genetics , Middle Aged , Phenotype , Positron-Emission TomographyABSTRACT
The authors present a case of a rare tumour of the eyelid sebaceous glands with an unfavourable prognosis, and emphasize the importance of carrying out histological examination of all eyelid neoformations to better identify the lesion and obtain an accurate diagnosis. The Authors discuss the histopathologic aspects of this case, and the findings in the literature.
Subject(s)
Adenocarcinoma, Sebaceous/pathology , Diagnostic Errors , Sebaceous Gland Neoplasms/pathology , Adenocarcinoma, Sebaceous/diagnosis , Adenocarcinoma, Sebaceous/surgery , Aged, 80 and over , Corneal Opacity/complications , Corneal Opacity/surgery , Eye Enucleation , Female , Granuloma/diagnosis , Humans , Iris Diseases/etiology , Iris Diseases/surgery , Postoperative Complications/diagnosis , Postoperative Complications/pathology , Postoperative Complications/surgery , Sebaceous Gland Neoplasms/diagnosis , Sebaceous Gland Neoplasms/surgeryABSTRACT
We describe a case of metachronous bilateral interstitial-cell tumor of the testis in a 54-year-old man with no evidence of endocrine symptoms. About 300 Leydig cell tumor cases have been reported in literature and only in 3% the tumor was bilateral. Rare examples have been reported in cryptorchid testis. In adult patients with Leydig cell tumor of the testis, endocrinologic signs occur in 20 per cent of cases and often precede the onset of a palpable testicular mass. Pathological aspects are discussed and a survey of the literature is reported.