Germline mosaicism in neurofibromatosis type 1 due to a paternally derived multi-exon deletion.

We report on the clinical and molecular features of a family in which neurofibromatosis type 1 (NF1) occurred in two of three siblings born to unaffected parents and in one granddaughter. Linkage analysis showed that the two affected siblings and the daughter of one of them shared the same paternal allele, whereas they had inherited different maternal alleles. We detected a disease-causing deletion (c.4773-3622-?_5749+?del) encompassing three NF1 gene exons in affected individuals. This mutation occurred on the paternally derived allele, arguing for a germline mosaicism in the probands' father. Real-time PCR showed that the mutation was present in about 10-17% of the paternal sperms. Current results confirm that germline mosaicism can explain the recurrence of NF1 in offspring of unaffected parents.

Concomitant right subscapular and left olecranon elastofibroma followed by inversion of the lesions: case report.

Elastofibroma is a benign, poorly circumscribed, tumor-like condition involving, in the vast majority of cases, the subscapular region of elderly individuals, though isolated cases have been seen in the deltoid muscle, infraolecranon area, hip, thigh and stomach. It is characterized by accumulated abnormal elastic fibres and is generally regarded as a reactive process, an unusual fibroblastic pseudotumor. Multiple elastofibromas have been reported to occur in the scapula and olecranon and in the scapula and ischium, whereas literature reports of multiple elastofibromas in the same patient are rare. The case of concomitant, asynchronous double elastofibroma in the same patient is described. A 69-year-old woman presented with right subscapular and left olecranon swelling associated with pain and a clicking sensation during certain arm movements. Some months later the patient developed asymptomatic left subscapular and right olecranon swelling. All the lesions, which were subsequently diagnosed as elastofibromas, were removed.

Health-related quality of life in patients with neurofibromatosis type 1. A survey of 129 Italian patients.

BACKGROUND/AIMS: Neurofibromatosis type 1 (NF1), a genetic condition most commonly characterized by the presence of dermal neurofibromas and café au lait macules, has a significant impact upon quality of life (QoL). The study aimed to assess the impact of NF1 on QoL. METHODS: A total of 129 patients with NF1 completed the study questionnaires in an Italian academic dermatological centre and a neurofibromatosis clinic at the University of Rome. RESULTS: All domains of general-health-related QoL were affected. Patients with serious cosmetic problems reported a greater impact on the emotional domain. CONCLUSION: In our study, the impact of the cosmetic features on QoL had the greatest importance. This survey demonstrates the usefulness of QoL measurements in supplementing clinical assessments.

NF1 gene analysis based on DHPLC.

The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. The majority of these mutations are private and rare, generating elevated allelic diversity with a restricted number of recurrent mutations. In this study, we have assessed the efficacy of denaturing high-performance liquid chromatography (DHPLC), for detecting mutation in the NF1 gene. DHPLC is a fast and highly sensitive technique based on the detection of heteroduplexes in PCR products by ion pair reverse-phase HPLC under partially denaturing conditions. We established theoretical conditions for DHPLC analysis of all coding exons and splice junctions of the NF1 gene using the WAVEmaker software version 4.1.40 and screened for mutations a panel of 40 unrelated NF1 patients (25 sporadic and 15 familial), genetically uncharacterized. Disruptive mutations were identified in 29 individuals with an overall mutation detection rate of 72.5%. The mutations included eight deletions (exons 4b, 7, 10a, 14, 26, and 31), one insertion (exon 8), nine nonsense mutation (exons 10a, 13, 23.1, 27a, 29, 31, and 36), six missense mutations (exons 15, 16, 17, 24, and 31), four splice errors (exons 11, 14, 36, and 40) and a complex rearrangement within exon 16. Eighteen (62%) of the identified disruptive mutations are novel. Seven unclassified and three previously reported polymorphisms were also detected. None of the missense mutations identified in this study were found after screening of 150 controls. Our results suggest that DHPLC provides an accurate method for the rapid identification of NF1 mutations.