Neurofibromatosis-1 (NF1) is an autosomal dominant disorder with marked variability of expression. Analysis of the NF1 gene (NF1) has detected a variety of mutations without any clear correlation with phenotype. However, deletions which remove all of NF1 have been reported in a small number of patients who have minor facial abnormalities, mental retardation, learning disabilities, and early or excessive burden of cutaneous or plexiform neurofibromas. The purpose of this study was to determine whether these phenotypic traits are associated with whole gene deletions. Out of 406 of our NF1 patients, 70 patients had manifestations previously associated with gene deletions. Thirty-five of these patients from 26 families were available for study. By fluorescence in situ hybridization (FISH) analysis, 4 were found to have deletions of the entire gene, including 2 sporadic cases, 1 familial case, and 1 case where family history could not be verified. In addition, the mother of the familial case was found to be mosaic for the deletion. Our results suggest that although large NF1 deletions occur with relatively high frequency in patients with certain findings, the presence of a deletion cannot be predicted solely on the basis of clinical phenotype.
Cytogenetic analysis was performed on peripheral blood lymphocyte cultures from 19 patients with mycosis fungoides (MF )/Sézary syndrome (SS) stimulated with either phytohemagglutinin, a conventional mitogen, or a combination of interleukin-2 (IL-2) plus IL-7. The use of both PHA-stimulated and IL-2 plus IL-7–stimulated cultures enhanced the ability to identify clonal abnormalities. Clonal abnormalities were observed in 11 patients (53%) including one with monosomy for the sex chromosome as the sole abnormality. Five of the 11 patients with clonal abnormalities had normal peripheral white blood cell counts, indicating detectability of clones in the absence of frankly leukemic disease. The presence of clonal abnormalities correlated with advanced stage disease and a significantly reduced survival duration from the time of cytogenetic studies. Clonal abnormalities involving chromosomes 1 and 8 were observed in six cases. In five cases with aberrations of chromosome 1, loss of material involved the region between 1p22 and 1p36. In an additional case, a reciprocal translocation involving 1p33 was observed. Clonal abnormalities involving chromosomes 10 and 17 were observed in 5 cases, clonal abnormalities involving chromosome 2 in 4 cases, and clonal abnormalities involving chromosomes 4, 5, 6, 9, 13, 15, 19, and 20 in 3 cases. In 2 cases a der(8)t(8; 17)(p11; q11) was observed. Regions of the genome that encode T-cell receptors were not involved in abnormalities. The region between 1p22 and 1p36 is identified as a region of the genome that requires detailed analysis toward the identification of potential gene(s) involved in the process of malignant transformation and/or progression in MF/SS.
Chronic lymphocytic leukemia (CLL) is recognized as a distinct entity. However, morphologic and immunophenotypic heterogeneity exist. Twenty-six patients with CLL were studied to investigate whether an association exists among peripheral blood karyotype, morphology and immunophenotype. Clonal cytogenetic abnormalities were detected in 14 patients (53%), using conventional karyotyping techniques in addition to fluorescence in situ hybridization (FISH) for chromosome 12. By FAB guidelines, 7 of the 8 patients (88%) with trisomy 12 had mixed cell morphology compared to only 3 of 18 (17%) without trisomy 12 (P = .004). One patient (12%) with trisomy 12 had lymphocyte morphology typical for CLL. Six of the eight (75%) with trisomy 12 had atypical immunophenotype including one or more of the following: strong CD20 expression, strong surface light chain expression, or absence of CD23 expression. Only 2 of the 18 patients (11%) without trisomy 12 had atypical immunophenotype (P = .005). None of the three patients with clonal structural abnormalities of chromosome 13q14 had mixed cell morphology or atypical immunophenotype. One of the 12 patients (8%) without clonal cytogenetic abnormalities had mixed cell morphology and one had atypical immunophenotype. This study suggests that a correlation exists among karyotype, morphology, and immunophenotype in CLL, and that CLL subgroups can be identified based on laboratory parameters. Although normal karyotypes or clonal structural abnormalities of 13q14 are associated with morphology and immunophenotype considered typical for CLL, trisomy 12 is associated with mixed cell morphology and atypical immunophenotype. These findings may have implications for evaluating variation in both disease course and response to emerging therapies.
We report on a case of an interstitial duplication of 11q in a patient with developmental delay and in his moderately delayed mother. Partial trisomy 11q is well documented in the literature with most cases involving the distal region of the long arm of chromosome 11. In almost all cases, this trisomy is associated with monosomy of the second chromosome involved in the parental translocation. The most common, partial 11q and 22q trisomy syndrome, is observed in offspring of t(11;22)(q23;q11.2) carriers from a 3:1 tertiary trisomic malsegregation. We found only two previous reports of pure partial trisomy 11q in the literature. Comparison of the clinical findings of our patient and another single published report of duplication in the same segment of chromosome 11 suggests that the duplication of this region manifests mild phenotypic abnormalities.
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