36 research outputs found
Differential allelic expression of SOS1 and hyperexpression of the activating SOS1 c.755C variant in a Noonan syndrome family
Noonan syndrome (NS) is a genetic condition characterized by congenital heart defects, short stature and characteristic facial features. We here present the case of a girl with moderate learning disabilities, delayed language development, craniofacial features and skin anomalies reminiscent of NS. After a mutation screening of the known NS genes PTPN11, SOS1, RAF1, KRAS, GRB2, BRAF and SHOC2 we found the heterozygous c.755T>C variant in SOS1 causing the p.I252T amino-acid substitution, which was considered possibly pathogenetic by bioinformatic predictions. The same variant was present in the proband's mother, displaying some NS features, and mateRNAl grandfather showing no NS traits, but also by a healthy subject in 1000 genomes project database without phenotype informations. The functional analysis revealed that SOS1 c.755C activated the RAS-ERK intracellular pathway, whereas no effects on RAC-JNK cascade have been detected. After a comparison between the sequence of SOS1 cDNA from peripheral blood and SOS1 genomic DNA, we showed for the first time a differential allelic expression of the SOS1 gene in healthy individuals, thus occurring as a physiologic condition. Interestingly, we found that the mutated allele C was 50% more expressed than the wild-type allele T in all familial carriers. The comparable amount of SOS1 mRNA between mutated individuals and the controls indicates that the variant does not affect SOS1 expression. The present study provides a first evidence of allelic imbalance of SOS1 and pinpoints this condition as a possible mechanism underlying a different penetrance of some SOS1-mutated alleles in unrelated carriers
Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with nonsyndromic mental retardation
Mental retardation (MR) is displayed by 57% of
NF1 patients with microdeletion syndrome as a result of
17q11.2 region haploinsufficiency. We considered the
cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1)
and oligodendrocyte-myelin glycoprotein (OMG) genes,
mapping in the NF1 microdeleted region, as candidate
genes for MR susceptibility. CDK5R1 encodes for a
neurone-specific activator of cyclin-dependent kinase 5
(CDK5) involved in neuronal migration during central
nervous system development. OMG encodes for an
inhibitor of neurite outgrowth by the binding to the
Nogo-66 receptor (RTN4R). CDK5R1 and OMG genes
are characterized by large 3\u2032 and 5\u2032 untranslated regions
(UTRs), where we predict the presence of several transcription/
translation regulatory elements. We screened
100 unrelated Italian patients affected by unspecific MR
for mutations in CDK5R1 and OMG coding regions and in
their 3\u2032 or 5\u2032 UTRs. Four novel mutations and two novel
polymorphisms for CDK5R1 and three novel mutations
for OMG were detected, including two missense changes
(c.323C>T; A108V in CDK5R1 and c.1222A>G; T408A
in OMG), one synonymous codon variant (c.532C>T;
L178L in CDK5R1), four variants in CDK5R1 3\u2032UTR and
two changes in OMG 5\u2032UTR. All the mutations were absent in 370 chromosomes from normal subjects. The
allelic frequencies of the two novel polymorphisms in
CDK5R1 3\u2032UTR were established in both 185 normal and
100 mentally retarded subjects. Prediction of mRNA and
protein secondary structures revealed that two changes
lead to putative structural alterations in the mutated
c.2254C>G CDK5R1 3\u2032UTR and in OMG T408A gene
product
MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury
Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury
Il cancro del fusto minaccia il melograno italiano
Diversi impianti di melograno stanno morendo a causa del fungo Coniella granati, patogeno per il quale è lecito attendersi una rapida diffusione