1,720,980 research outputs found
Cardio-Facio-cutaneous syndrome: phenotypic variability and differential diagnosis in 3 cases with de novo BRAF mutations
No full textCardio-facio-cutaenous (CFC) syndrome is a developmental disorder causing mental retardation and multiple congenital anomalies, including craniofacial, ectodermal, cardiac and musculoskeletal defects. Mutation of several genes in the RAS/MAPK (mitogen activated protein kinase) signaling pathway, most commonly BRAF, results in CFC syndrome. In this study, we report 3 new patients with CFC syndrome caused by mutation of BRAF. These patients differed in neurological impariment, craniofacial features and cardiac defects, while they shared relatively similar ectodermal and skeletal anomalies. They also displayed some overlapping featrues with Costello syndrome, another RAS/MAPK pathway disorder. Our findings highlight the clinical variability of CFC syndrome, with respect to severity and pattern of the affected organs, as well as the phenotypic overlap with the Costello syndrom
Unexpected finding of paternal premutation of the fragile X FMR1 gene in a female fetus of a premutation carrier mother
No full textAssisted reproductive technology and congenital overgrowth:some speculations on a case of Pallister-Killian syndrome
No full textWe report on a boy with Pallister-Killian syndrome (PKS) who was conceived by assisted reproductive technology (ART), specifically in vitro fertilization (IVF) with parents' gametes. A prenatal diagnosis performed elsewhere by CVS failed to detect the presence of the isochromosome 12p that was demonstrated postnatally in approximately 50% of cultured skin fibroblasts. Given that the patient did not show the congenital overgrowth typical of PKS, we speculate that ART might have restricted overgrowth in this particular case. More broadly, we hypothesize that overgrowth might protect from early demise fetuses conceived by ART, a technology known to cause low and very low birth weight
Simpson–Golabi–Behmel syndrome in a female: A case report and an unsolved issue
No full textSimpson–Golabi–Behmel syndrome is an X-linked recessive overgrowth condition caused by alterations in GPC3 gene, encoding for the cell surface receptor glypican 3, whose clinical manifestations in affected males are well known. Conversely, there is little information regarding affected females, with very few reported cases, and a clinical definition of this phenotype is still lacking. In the present report we describe an additional case, the first to receive a primary molecular diagnosis based on strong clinical suspicion. Possible explanations for full clinical expression of X-linked recessive conditions in females include several mechanisms, such as skewed X inactivation or homozygosity/compound heterozygosity of the causal mutation. Both of these were excluded in our case. Given that the possibility of full expression of SGBS in females is now firmly established, we recommend that GPC3 analysis be performed in all suggestive female cases. © 2016 Wiley Periodicals, Inc
A unique case of reversion to normal size of a maternal premutation FMR1 allele in a normal boy
No full textFragile X syndrome (FXS) is caused mostly by expansion and subsequent methylation of the CGG repeat in the 5'UTR of the FMR1 gene, resulting in silencing of the gene, absence of FMRP and development of the FXS phenotype. The expansion also predisposes the CGG repeat and the flanking regions to further instability that may lead to mosaics between a full mutation and a premutation or, rarely, a normal or deleted allele. Here, we report on a 10-year-old boy with no FXS phenotype, who has a normal CGG tract, although he inherited the maternal expanded allele that causes FXS in his two brothers. Southern blotting demonstrated that the mother carries a premutation allele ( approximately 190 CGG), whereas the propositus shows a normal 5.2 kb fragment after HindIII digestion and a smaller 2.2 kb fragment after double HindIII-EagI digestion, without any apparent mosaicism in peripheral blood leukocytes. PCR and sequence analysis of the FMR1 5'UTR revealed an allele of 43 repeats, with two interspersed AGG triplets in position 10 and 25 and an exceptional CCG triplet in position 17. This latter creates an abnormal EagI site compatible with the smaller 2.2 kb fragment observed with Southern blotting. Haplotype analysis proved that the rearranged allele originated from the maternal expanded allele. To the best of our knowledge, this is the first non-mosaic case of reduction in the CGG tract of the FMR1 gene, resulting in a normal allele
Quantitative analysis of DNA demethylation and transcriptional reactivation of the FMR1gene in fragile X cells treated with 5-aza-deoxycitidine
No full textMODULATION OF METHYLATION IN THE FMR-1 PROMOTER REGION AFTER LONG TERM TREATMENT WITH L-CARNITINE AND ACETYL-L-CARNITINE
No full textA new single-nucleotide deletion of PMP22 in an HNPP family without recurrent palsies.
No full textIn this study we describe four patients from the same kindred who were affected
by an autosomal-dominantly inherited peripheral neuropathy. They presented an
unusual combination of clinical, electrophysiological, and pathological findings
in association with a new mutation of the PMP22 gene. Clinically, three patients
had carpal tunnel syndrome symptoms and one patient had late-onset peroneal
atrophy. Motor and sensory nerve conduction velocities were reduced without focal
slowing at entrapment sites. Nerve biopsy disclosed diffuse hypomyelination with
focal thickening of the myelin sheath in some fibers. Sequence analysis of the
PMP22 gene showed a single-nucleotide deletion (227delG) in the affected
patients. This mutation, which has not been reported previously, leads to an open
reading frame shift and probably to a truncated and unstable PMP22 protein. We
conclude that this novel 227delG mutation of PMP22 gives a mild form of
hereditary neuropathy with liability to pressure palsy with atypical clinical and
electrophysiological findings
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