Young AL, Kellermayer R, Szigeti R et al.CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet 70:246-249
Department of Dermatology, Columbia University, New York, NY 10032, USA.Clinical Genetics (Impact Factor: 3.93). 10/2006; 70(3):246-9. DOI: 10.1111/j.1399-0004.2006.00667.x
Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial trichoepithelioma (MFT), originally described as distinct inherited disorders, are characterized by a variety of skin appendage neoplasms. Mutations in the CYLD gene are found in individuals with these syndromes. We describe a single family with affected members exhibiting either the FC or the MFT phenotypes associated with a mutation in the CYLD gene. These findings support the notion that BSS, FC, and MFT represent phenotypic variation of a single defect. Of interest, one of the affected individuals described in this report exhibits a severe phenotype illustrating the morbidity of the disorder.
- [Show abstract] [Hide abstract]
ABSTRACT: Hereditary paraganglioma, Gorlin-Goltz syndrome and Fanconi anemia are among the rare hereditary tumor syndromes of the head and neck. Patients with hereditary paraganglioma often develop multiple tumors of the glomus caroticum and glomus jugulotympanicum. The corresponding genetic defects of the mitochondrial succinate dehydrogenase complex induce autonomous tumor cell growth. In patients with Gorlin-Goltz syndrome basal cell carcinomas and keratocystic odontogenic tumors usually occur much earlier than in patients with sporadic tumors. The associated germline mutations are located in the patched gene which is a modulator of the cell cycle. Fanconi anemia represents a chromosomal instability syndrome which is characterized by early onset of pancytopenia, i.e. bone marrow failure and subsequent development of acute myeloid leukemia and/or squamous cell carcinomas, especially of the head and neck. A total of 13 different gene clusters have been identified in 2 DNA associated complexes which play an important role in DNA repair mechanisms.
- [Show abstract] [Hide abstract]
ABSTRACT: With the development of new approaches to transplantation therapy, such as those building upon the potential found in stem cells, it is vital to pursue a clear understanding of transplantation risks. Allogeneic transplantation presents risk for the transmission of disease of various types, including genetic disease. Predisposition to develop cancer is a feature of numerous genetic disorders, and it may be transmissible by transplantation. Some genetic disorders predisposing to cancer are remarkably common, either worldwide or in specific populations, and they could pose significant risk. Hence, to reduce risk to recipients, there is reason to exclude from donation those potential donors (including embryos) harboring certain germ-line mutations. However, the frequent absence of readily identifiable features might confound the effort to exclude those who harbor mutation. Thus, it is also important to consider the magnitude of risk that they represent. For some disorders, life-threatening cancer is highly likely to develop in those individuals born with germ-line mutation, but whether recipients would face the same risk from transplanted mutation is not always evident. Given the diversity of pathways that lead to cancer, there may be diverse factors that impact the likelihood for cancer to develop in the recipient, with some factors decreasing and others increasing the risk. One factor of special concern is the possibility that manipulation of donor cells, prior to transplantation, might introduce additional genetic or epigenetic abnormality, thereby increasing the risk.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.