1/5. growth regulation, acid sphingomyelinase gene and genomic imprinting: lessons from an experiment of nature.The author investigated the possible role of acid sphingomyelinase (ASM) gene (SMPD1) in the regulation of growth, in connection with an experiment of nature. The association of a decreased ASM activity and an overgrowth disorder, beckwith-wiedemann syndrome (BWS) with hemihypertrophy has been described at a 23 months old boy in a recent case report (Rethy et al, in this issue). ASM catalyses the production of ceramide, a key molecule of apoptosis, from sphingomyelin. Based on these data it is suggested that the ASM gene (SMPD1) can suppress/counterbalance the anti-apoptotic effects of BWSrelated growth-promoters, like IGF-II, under normal circumstances. Recent literary data support this view. ASM deficient lymphoblasts derived from patients with Niemann-Pick disease (NPD) fail to undergo apoptosis in response to external signals and Fas cross-linking. BWS-related genes are considered to be regulated by genomic imprinting. Therefore the author compared some characteristics of both SMPD1 and imprinted genes. The analyzed features of SMPD1 gene (few and small introns, Alu 1 repeat element, CC-rich regulatory region, alternative splicing) are characteristic to imprinted genes. Hemihypertrophy, mentioned in the referred BWS-case, is distinctive to the involvement of the maternal allele of the second BWS chromosomal region (BWSCR2) at 11p15.3. The SMPDI gene has been localized just distal to the B05 breakpoint of BWSCR2. Furthermore, in BWS-associated tumors, the loss of heterozygosity (LOH) found on 11p15 was always maternal. Thus, in the case referred to with ASM deficiency the maternal allele has certainly been effected. These conclusions are in accordance with the 'cluster-model of imprinting' as well as with the conflict theory of imprinting. Taken together, the above mentioned clinical and experimental data suggest that SMPD1, most likely at 11p15.4, is an imprinted, maternally expressed, BWS- and apoptosis-related growth suppressor gene. Further studies are necessary to prove this hypothesis.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/5. hepatoblastoma associated with beckwith-wiedemann syndrome and hemihypertrophy.Both beckwith-wiedemann syndrome (BWS) and hemihypertrophy (HH) have been recognized to be overgrowth syndromes associated with an increased risk of cancer. We report an infant with hepatoblastoma associated with both BWS and HH in whom high serum alpha-fetoprotein (AFP) levels persisted even after complete tumor resection with no tumor recurrence. This phenomenon might be partly due to the nature of the proliferative disease. It is important to recognize that in some infants with BWS prolonged high serum AFP levels mimic the existence of a tumor, and that treatment should be based not only on AFP measurement, but also on repeated radiologic imaging.- - - - - - - - - - ranking = 0.2keywords = nature (Clic here for more details about this article) |
3/5. Bilateral adrenal cysts and ectopic pancreatic tissue in beckwith-wiedemann syndrome: is a conservative approach acceptable?beckwith-wiedemann syndrome is a common overgrowth syndrome associated with an increased risk of neoplasias which might be explained by the nature and localization of the genetic defect. While malignant tumors are often associated with hemihypertrophy, benign tumors are also found. We report a patient with the typical features of beckwith-wiedemann syndrome with two histologically different abdominal tumors, bilateral cystic adrenals and ectopic pancreatic tissue present at birth. In both tumors no malignancy could be detected. Ectopic pancreatic tissue is rarely seen and has been described in beckwith-wiedemann syndrome only once. After extirpation of the ectopic pancreatic tissue the cystic adrenals were left in situ since macroscopically no normal adrenal tissue could be identified and separated. Regular ultrasound examinations revealed complete resolution of the cystic adrenals within 24 months. Thus it seems that a conservative approach in selected tumors associated with the beckwith-wiedemann syndrome might be acceptable.- - - - - - - - - - ranking = 0.2keywords = nature (Clic here for more details about this article) |
4/5. Paternally inherited duplications of 11p15.5 and beckwith-wiedemann syndrome.We present a three generation family in which a father and son have a balanced chromosome translocation between the short arms of chromosomes 5 and 11 (karyotype 46,XY,t(5;11)(p15.3;p15.3)). Two family members have inherited the unbalanced products of this translocation and are trisomic for chromosome 11p15.3-->pter and monosomic for chromosome 5p15.3-->pter (karyotype 46,XY,der(5)t(5;11)(p15.3;p15.3)pat). Paternally derived duplications of 11p15.5 are associated with beckwith-wiedemann syndrome (BWS) and both family members trisomic for 11p15.5 had prenatal overgrowth (birth weights >97th centile), macroglossia, coarse facial features, and broad hands. We review the clinical features of BWS patients who have a paternally derived duplication of 11p15.5 and provide evidence for a distinct pattern of dysmorphic features in those with this chromosome duplication. Interestingly, our family is the fifth unrelated family to be reported with a balanced reciprocal translocation between the short arms of chromosomes 5 and 11. The apparently non-random nature of this particular chromosome translocation is suggestive of sequence homology between the two chromosome regions involved in the translocation.- - - - - - - - - - ranking = 0.2keywords = nature (Clic here for more details about this article) |
5/5. Characterization of the breakpoints in unbalanced t(5;11)(p15;p15) constitutional chromosome translocations in two patients with beckwith-wiedemann syndrome using fluorescence in situ hybridisation.Although the majority of patients with beckwith-wiedemann syndrome (BWS) have a normal karyotype, the study of those rare patients with a cytogenetic abnormality has given considerable insight into the genetics of this condition. The karyotypic abnormalities found include partial chromosome duplications of paternal origin and maternally derived translocations which usually involve the 11p15 region and provide one of the lines of evidence for the location of the BWS gene(s). Because the extent of the duplicated region in these patients is variable, the phenotypic expression of BWS is presumably due to the presence of a common duplicated region. Two unrelated patients with BWS were both noted to have a similar unbalanced t(5;11)(p15;p14) translocation. The parents in both families were unaffected but both fathers carried a balanced translocation involving the same chromosomes. Since the extent and nature of the duplication apparently determines the complex phenotypes seen in these patients, we undertook a detailed analysis of the extent of the triplicated region using fluorescent in situ hybrisation (FISH). Despite having markedly different phenotypes and presenting in disimilar ways the two patients had apparently identical duplication breakpoints.- - - - - - - - - - ranking = 0.2keywords = nature (Clic here for more details about this article) |