1/4. cavernous sinus thrombophlebitis in nijmegen breakage syndrome.The aim of the study was to present rarely reported neurologic complications in nijmegen breakage syndrome. A 13-year-old female was referred because of chronic progressive headaches. There were dysmorphic features on physical examination, which suggested a diagnosis of chromosomal instability syndrome. The results of genetic and immunologic examinations confirmed the diagnosis. Cerebral magnetic resonance imaging revealed an 8 mm thickening of the meninges over the left hemisphere, corresponding with a chronic inflammatory condition, and symptoms of left cavernous thrombophlebitis were detected. cerebrospinal fluid examination and an infusion test demonstrated disorders in its absorption. Antibiotic, anticoagulant and cerebral edema treatment was given and after 1 week improvement was observed. Regression of symptoms occurred after 14 days.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/4. Familial MCA/MR syndrome due to inherited submicroscopic translocation t(18;21)(q22.1q21.3) with breakpoint at the down syndrome critical region.We report three generation family that includes two patients with severe mental retardation and additional anomalies who have been studied, clinically, cytogenetically, and molecular cytogenetically. A clinical diagnosis could not be made in the propositus, but facial anomalies of down syndrome (DS) were recognized in the maternal uncle of the propositus. In view of a strong family history of recurrent miscarriage, a familial translocation was highly suggestive. Standard cytogenetic analysis did not reveal any abnormalities. fluorescence in situ hybridization (FISH) using subtelomeric dna probes identified a familial cryptic translocation of chromosomes 18 and 21, resulting in partial trisomy 21 and partial monosomy 18q in both patients. FISH analysis of obligate carriers demonstrated a balanced translocation between the terminal parts of 18q and 21q. Including this family, a total of six different familial cases with cryptic or subtle subtelomeric translocations of chromosome 21q has been reported, of which three involved terminal parts of chromosome 18q. The remarkable similarity of the chromosomal breakpoints of our patients and the described families prompted us to refine the breakpoints and to discuss phenotypic differences between these patients. Our results reinforce the role of cryptic subtelomeric rearrangements in patients with mental retardation associated with physical anomalies and stress the importance of FISH technology to supplement routine cytogenetics.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/4. Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome.3p deletion syndrome is a rare contiguous-gene disorder involving the loss of the telomeric portion of the short arm of chromosome 3 and characterized by developmental delay, growth retardation, and dysmorphic features. All reported cases have involved, at a minimum, the deletion of chromosome 3 telomeric to the band 3p25.3. Despite the presence of several genes in this region that are involved in neural development, a causative relationship between a particular transcript and the observed clinical manifestations has remained elusive. We have identified a child with characteristic physical features of 3p deletion syndrome and both verbal and nonverbal developmental delay who carries a de novo balanced translocation involving chromosomes 3 and 10. Fine mapping of this rearrangement demonstrates that the translocation breakpoint on chromosome 3 falls within the recently identified minimal candidate region for 3p deletion syndrome and disrupts the Contactin 4 (CNTN4) mRNA transcript at 3p26.2-3p26.3. This transcript (also known as BIG-2) is a member of the immunoglobulin super family of neuronal cell adhesion molecules involved in axon growth, guidance, and fasciculation in the central nervous system (CNS). Our results demonstrate the association of CNTN4 disruption with the 3p deletion syndrome phenotype and strongly suggest a causal relationship. These findings point to an important role for CNTN4 in normal and abnormal CNS development.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
4/4. Disruption of TCBA1 associated with a de novo t(1;6)(q32.2;q22.3) presenting in a child with developmental delay and recurrent infections.A boy with developmental delay, particularly of speech, a distinct face, antineutrophil cytoplasmic antibodies, and recurrent infections was found to have an apparently balanced de novo t(1;6)(q32.3;q22.3) translocation. Fluorescent in situ hybridisation with BAC/PAC clones and long range polymerase chain reaction products assessed in the human genome sequence localised the chromosome 1 breakpoint to a 9.8 kb segment within a hypothetical gene, LOC388735, and the chromosome 6 breakpoint to a 12.8 kb segment in intron 4 of the T-cell lymphoma breakpoint-associated target 1 (TCBA1) gene. Disruption and/or formation of TCBA1 fusion genes in T cell lymphoma and leukaemia cell lines suggests a role for this gene in tumorigenesis. The isolated mouse Tcba1 gene shows 91% amino acid sequence similarity with human TCBA1. It is expressed in fetal and adult brain and with lower levels in liver and testis. The human gene has been reported to be expressed exclusively in brain and thymus. Reduced TCBA1 expression in brain and thymus may explain at least some of the symptoms in this patient. It is concluded that germline alterations of the TCBA1 gene are associated with developmental delay and typical physical features.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |