Ring chromosomes are uncommon cytogenetic findings and are often associated with clinical features overlapping the phenotype of patients with terminal deletions of the corresponding chromosome.... Show moreRing chromosomes are uncommon cytogenetic findings and are often associated with clinical features overlapping the phenotype of patients with terminal deletions of the corresponding chromosome. Most of the ring chromosomes arise sporadically and parental transmission is rarely observed. We report five patients carrying a ring chromosome 11, with three of the patients belonging to the same family. SNP array analysis was performed to characterize the different ring chromosomes and the clinical phenotypes were compared with previously reported patients with ring chromosome 11. Show less
Nielsen, M.; Vermont, C.L.; Aten, E.; Ruivenkamp, C.A.L.; Herrewegen, F. van; Santen, G.W.E.; Breuning, M.H. 2012
Genomic DNA of three patients, born as healthy carriers and developing a late-onset severe transfusion-dependent beta-thalassemia major was studied by high density genome wide SNP array analysis. A... Show moreGenomic DNA of three patients, born as healthy carriers and developing a late-onset severe transfusion-dependent beta-thalassemia major was studied by high density genome wide SNP array analysis. A mosaic loss of heterozygosity for almost the entire 11p was found not attributable to deletions, but involving mosaicism for segmental paternal isodisomy of 11p. Mitotic recombination leading to mosaic segmental uniparental isodisomy on chromosome 11p in multiple tissues has been described as a molecular disease mechanism for a subset of sporadic Beckwith-Wiedemann syndrome cases. A similar mechanism also seems to be involved in causing late-onset disease in carriers of recessive mutations in other genes located in 11p, such as late-onset beta-thalassemia major and sickle cell disease. We suggest that the the loss of maternally imprinted IGF-2 and H19 genes may account for the selective advantage of hematopoietic cells containing this segmental paternal isodisomy of 11p carrying the beta-thalassemia mutation. Show less
Several genes involved in the familial appearance of thoracic aortic aneurysms and dissections (FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new... Show moreSeveral genes involved in the familial appearance of thoracic aortic aneurysms and dissections (FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new syndromic form of aortic aneurysms and dissections associated with skeletal abnormalities. We discovered a small interstitial deletion of chromosome 15, leading to disruption of SMAD3, in a boy with mild mental retardation, behavioral problems and revealed features of the aneurysms-osteoarthritis syndrome (AOS). Several family members carried the same deletion and showed features including aortic aneurysms and a dissection. This finding demonstrates that haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections, and the skeletal abnormalities that form part of the aneurysms-osteoarthritis syndrome. Interestingly, the identification of this familial deletion is an example of an unanticipated result of a genomic microarray and led to the discovery of important but unrelated serious aortic disease in the proband and family members. Show less
