1,720,998 research outputs found
New case of the Richieri-Costa/Guion-Almeida syndrome
No full textWe describe a boy with multiple congenital anomalies/mental retardation (MCA/MR) syndrome. He has growth retardation, microbrachycephaly, coloboma of the iris, and typical facial anomalies including cleft lip/palate. This phenotype overlaps with that described by Richieri-Costa and Guion-Almeida in three Brazilian brothers. The new patient provides further evidence of the existence of this rare clinical entity
Developmental abnormalities and cancer predisposition in neurofibromatosis type 1
No full textNeurofibromatosis type 1 (NF1) is a developmental and cancer predisposing syndrome resulting from haploinsufficiency or alteration in neurofibromin, a multifunctional protein that acts in various signaling pathways affecting morphogenetic processes and cell proliferation. Neurofibromin deficiency deregulates Ras/Raf/MEK/ERK and Ras/PI3K/AKT/PKB/mTOR signaling networks and intersected pathways including the cAMP-dependent protein kinase A (PKA) and the Rho-cofillin which acts on actin cytoskeleton reorganization, cell motility and adhesion. As the neurofibromin-mediated pathways are associated with biological effects depending on the cell lineage, deregulation induced by NF1 mutation clearly has cell type-specific effects. This review summarizes our increasing knowledge of NF1 as a disease rooted in defective developmental mechanisms that can also influence the potential for malignant growth. The cardinal features of NF1 patients, at birth and during life involve the cardiovascular, connective/skeletal and central nervous systems, as they reflect the NF1 mutation sensitivity of cell lineages committed to specifying these systems during embryonic development. A switch to neoplastic transformation may also occur in both the prenatal and postnatal life in cancer initiating cells of defined lineages, with the cooperation of a genetically and epigenetically modified tumor microenvironment. We emphasize how much of our current knowledge of the pathomechanisms of NF1 clinical signs and cancer has come from engineered mouse models and in vitro primary cells and cell lines exposed to inhibitors of signaling molecules. Advances in our knowledge of the developmental defects primed by the loss neurofibromin should reveal further associations between given NF1 mutations and tissue-specific symptoms, thus improving the clinical management of the patients
NF1 exon 7 skipping by disruption of exonic splice enhancers (ESEs) in neurofibromatosis 1
No full textThe underestimates of NF1 gene mutations in neurofibromatosis 1 (NF1) have been attributed to the large size of the NF1 gene, the considerable frequency of gross deletions and the common occurrence of splicing defects that are only detectable by cDNA analysis. We here report on a patient with severe NF1 showing at RT-PCR analysis the expected fragment from exon 4b to 8 together with a shortened one with the in-frame skipping of exon 7. Sequencing of the corresponding genomic fragment revealed a G→A transition and a C→A transversion at nucleotide positions 57 and 58 of the 174-bp long exon 7, neither of which was present in the proband's parents or 50 healthy controls. No other variation was found in the entire NF1 coding sequence. The use of previously established sequence matrices for the scoring of putative ESE motifs showed that the adjacent silent and missense mutations are located within highly conserved overlapping stretches of seven nucleotides with a close similarity to the ESE-specific consensus sequences recognised by the SC35 and SF2/ASF SR proteins. The combined occurrence of both consecutive alterations decreases the motif score for both SF2/ASF and SC35 below then- threshold levels. As the aberrant transcript is consistently expressed, a protein lacking 58 amino acids is predicted. Thus the contiguous internal exon 7 mutations are suggested to cause exon 7 skipping as a result of the mis-splicing caused by abrogation of functional ESEs
Refined FISH characterization of a de novo 1p22-p36.2 paracentric inversion and associated 1p21-22 deletion in a patient with signs of 1p36 microdeletion syndrome
No full textWe report on a 10-year-old boy presenting with obesity, moderate mental retardation, large anterior fontanelle at birth, mild physical anomalies including mid-face hypoplasia, deep-set eyes, long philtrum, and small mouth. He was found to carry a paracentric inversion inv(1)(p22p36.2) associated with a 10 cM deletion at the proximal breakpoint. By YAC FISH, the boundaries of the deletion were established at IB1028 (1p21) and WI-5166 (1p22) STSs contained in YACs 781E8 and 954F6, respectively. This large region, covering about 10 cM, contains the COL11A1 and AMY2B genes, whose haploinsufficiency does not seem to contribute significantly to the clinical phenotype. On the other hand, the patient's clinical manifestations, also including visual problems and moderate mental retardation, are those typically observed in the 1p36 deletion syndrome. Refined mapping of the telomeric 1p36.2 inversion breakpoint was obtained by FISH of a PAC contig constructed to encompass this subinterval of the 1p36 microdeletion syndrome region. PACs 1024B10 and 884E7 were found to span the breakpoint, suggesting that the clinical signs of the 1p36 microdeletion syndrome might be due to disruption of a sequence lying at 1p36.2
FISH characterization of a supernumerary r(1)(::cen-->q22::q22-->sq21::) chromosome associated with multiple anomalies and bilateral cataracts
No full textWe describe the case of a 15-year-old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21-22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI-7732 and WI-607, with WI-7396 and WI-8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataractogenesis
Diagnosi di S. di Alagille in età adulta e risconto di una nuova mutazione del gene JAG1
No full textPatient with large 17p11.2 deletion presenting with Smith-Magenis syndrome and Joubert syndrome phenotype
No full textWe report on a 22-year-old woman carrying a del(17)(p11.2p12) and presenting with the clinical manifestations of both Smith-Magenis syndrome (SMS) and Joubert syndrome (JS). Her facial anomalies, brachydactyly, severe mental retardation, and self-injuring behavior could be attributed to SMS, whereas the cerebellar vermis hypoplasia, hypotonia, ataxic gait, developmental delay, and abnormal respiratory pattern were suggestive of JS. By fluorescent in situ hybridization analyses with Yeast Artificial Chromosomes (YAC) mapping to the 17p11.2 region, as well as locus-specific probes generated through a novel procedure, we could establish that the deletion encompasses a 4-Mb interval with centromeric and telomeric breakpoints at loci D17S793 and D17S953, the latter close to the locus Charcot Marie Tooth 1A (CMT1A)-REP. The deletion differs from that commonly found in SMS in its telomeric boundary, which is more distal than usually observed. The presence of JS phenotype in our patient and the detection of an unusual SMS deletion might suggest the presence of a JS gene in close proximity to the SMS locus
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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