A case of Brooke-Spiegler syndrome with a novel mutation in the CYLD gene in a patient with aggressive non-Hodgkin's lymphoma.

PURPOSE: Brooke-Spiegler syndrome (BSS, familial cylindromatosis) is a rare hereditary disease characterized by multiple tumors of the skin appendages predominantly located in the head and neck region, such as cylindromas, trichoepitheliomas, or spiradenomas. It is caused by an autosomal dominant mutation in the CYLD gene, mapped on chromosome 16q12-13. Association with secondary malignant neoplasms has been reported. Until now 51 different mutations in 73 families have been reported; 41 % of them constitute frameshift mutations, resulting in an interruption of the expression of the gene product CYLD. CYLD is a deubiquitinating enzyme and plays an important role in (NF)-κB pathway signaling, a central pathway for apoptosis regulation. Mutation-induced loss of function leads to constitutive activation of NF-κB. METHODS: Here, we report the case of a 48-year-old female patient diagnosed with an abdominal aggressive non-Hodgkin's lymphoma. The patient presented with multiple cylindromas of the capillitium. The patient's mother also has a mild form of late-onset cylindromas. Due to the typical clinical features indicating BSS, genotyping from peripheral blood was performed. A c.2465insAACA mutation in exon 17 of the CYLD gene, leading to a frameshift, was detected in the patient and in the patient's mother. RESULTS/CONCLUSIONS: This is the first description of this hereditary mutation in exon 17 of the CYLD gene. There have been several reports on patients with CYLD mutations and different types of malignancies. However, a coincidence with aggressive non-Hodgkin's lymphoma has not been reported yet.

Identification of a de novo inv dup(X)(pter--> q22) by multicolor banding in a girl with Turner syndrome.

We report on a 23-year-old girl with short stature, short and wide neck, low posterior hairline, hypogonadism, underdeveloped breasts, infantile uterus, ovaries not visualized, and primary amenorrhea. Cytogenetic G-banding analysis revealed a mosaic karyotype of 46,X,dup(X)(q22)[35]/45,X[15], confirming the clinical suspicion of Turner syndrome. Molecular cytogenetics using a multicolor banding probe set for the X-chromosome characterized an inverted dup(X). The karyotype of the patient was therefore interpreted as 46,X,inv dup(X) (pter --> q22::q22 --> pter). This patient had a mosaic Turner syndrome with a cell line comprising partial trisomy Xpter to Xq22 and partial monosomy Xq22 to Xqter.

Multicolor fluorescence in situ hybridization (FISH) applied to FISH-banding.

During the last decade not only multicolor fluorescence in situ hybridization (FISH) using whole chromosome paints as probes, but also numerous chromosome banding techniques based on FISH have been developed for the human and for the murine genome. This review focuses on such FISH-banding techniques, which were recently defined as 'any kind of FISH technique, which provide the possibility to characterize simultaneously several chromosomal subregions smaller than a chromosome arm. FISH-banding methods fitting that definition may have quite different characteristics, but share the ability to produce a DNA-specific chromosomal banding'. While the standard chromosome banding techniques like GTG lead to a protein-related black and white banding pattern, FISH-banding techniques are DNA-specific, more colorful and, thus, more informative. For some, even high-resolution FISH-banding techniques the development is complete and they can be used for whole genome hybridizations in one step. Other FISH-banding methods are only available for selected chromosomes and/or are still under development. FISH-banding methods have successfully been applied in research in evolution- and radiation-biology, as well as in studies on the nuclear architecture. Moreover, their suitability for diagnostic purposes has been proven in prenatal, postnatal and tumor cytogenetics, indicating that they are an important tool with the potential to partly replace the conventional banding techniques in the future.