1/3. A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy.Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene -/- mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/3. Blastoid mantle cell lymphoma: evidence for nonrandom cytogenetic abnormalities additional to t(11;14) and generation of a mouse model.Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32), which is associated with cyclin d1 hyperexpression and a poor prognosis. MCL cases have been shown to progress to a more aggressive disease but the molecular events responsible of this phenomenon have not been determined. We have established two cell lines from the pleural effusions of two patients with MCL that we have used for further cytogenetic characterization to better define the incidence and nature of secondary chromosome abnormalities using multicolor fluorescence in situ hybridization, whole chromosome paint, and specific probes. Both cell lines grew independently without growth factors. Using CCND1/IGH-specific probes, patient UPN1 was found to have a masked t(11;14). Numerous and complex chromosomal abnormalities were found in both cell lines affecting chromosomes 2, 8, 13, 18, 22, X, and Y. These abnormalities included 8p losses, suggesting the presence of an anti-oncogene in this region, rearrangements of 8q24, MYC gene, and translocations involving 8, X, and Y chromosomes, which might be significant in the pathogenesis of MCL progression. The use of the cell lines (UPN1) allowed us to generate a mouse model of human MCL, mimicking a disseminated lymphoma and leading to the death of the animals in 4 weeks. This blastoid MCL model could be of major interest to determine molecular events involved in MCL progression, allowing isolation of involved genes and their functional characterization, and to study the effects of new chemotherapy regimens in mouse models.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/3. down syndrome--a gene dosage disease caused by trisomy of genes within a small segment of the long arm of chromosome 21, exemplified by the study of effects from the superoxide-dismutase type 1 (SOD-1) gene.down syndrome (DS), the most common postnatally viable human autosomal chromosomal abnormality is caused by trisomy for chromosome 21. The mechanism whereby the supernumerary chromosome 21 contributes to the pathology of DS remains elusive. There are, however, several evidences that DS is a gene dosage disease. This means that overproduction of certain proteins, encoded by normal genes on the extra chromosome, distorts the delicate balance of some biochemical pathways that are important for proper development and function of the organs affected in DS. It has been shown that only the distal segment of the long arm of chromosome 21 is involved in the pathogenesis of DS. Great efforts to define this "DS specific" segment are made today, with the aim to find the "DS responsible" genes. It is suggested that as few as 10-20 genes might be responsible for the DS phenotype. We will report from a world-wide collaboration study and especially the result from one single patient. It is a woman with a characteristic phenotype of DS, but with microscopically normal karyotype. She had a sister with DS, who is dead. The parents were related, why an autosomal recessive disorder is suspected. Autoradiograms of quantitative Southern blots of DNAs from the patient and her parents were analyzed after hybridization with unique dna sequences regionally mapped on chromosome 21. The patient seems to have three alleles at the VTNR-polymorphism in the Col6A1 gene, one copy from the father and two copies from the mother. The Col6A1 gene is mapped at the very distal segment of the long arm of chromosome 21 (21q22.3). She has only two alleles of all loci analyzed proximal to Col6A1. This might indicate that she has trisomy only for the very distal part of band 21q22.3. It is, however, not enough to find the genes within the "DS specific" segment. The metabolic gene dosage effects from these genes must be evaluated. Although several genes have been mapped on chromosome 21, not one single feature of DS has been proved to be an effect of any single gene. As an example of the difficulties to assign features of DS to chromosome 21 specific genes the gene dosage effects of the superoxide dismutase type I (SOD-1) will be presented.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |