PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression ...has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN.
Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It is characterized by germ cell loss and other variable clinical features, including autoimmunity. The sex-determining ...region of Y (SRY)-box 13 (Sox13) gene is expressed in mouse spermatogonia. In addition, it has been identified as islet cell autoantigen 12 (ICA12), which is involved in the pathogenesis of autoimmune diseases, including type 1 diabetes mellitus (DM) and primary biliary cirrhosis. Sox13 expression has never been investigated in patients with KS. In this age-matched, case-control study performed on ten patients with KS and ten controls, we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls. This finding might be consistent with the germ cell loss typical of patients with KS. However, the role of Sox13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.
The authors report on a boy with dyslexia and attention deficit hyperactivity disorder. A protocol of standardized tests assessed the neuroadaptive profile, allowing deep neuropsychiatric ...phenotyping. In addition to the diagnosis of dyslexia and attention deficit hyperactivity disorder, such methodology led to endeavor cognitive, adaptive, and academic skills. Chromosomal microarray analysis detected a 452.4 Kb de novo heterozygous microdeletion in chromosomal region 1p34.3, including seven OMIM genes. The authors took a thorough evaluation of the association to the phenotype of the deleted genes. Further reports could strengthen such association.
To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The ...smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which
,
,
,
and
are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only
,
and
genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that
is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of
and better define how the two contiguous genes,
and
, might contribute to the clinical phenotype.
Mitochondrial tRNASer(UCN) is considered a hot-spot for non-syndromic and aminoglycoside-induced hearing loss. However, many patients have been described with more extensive neurological diseases, ...mainly including epilepsy, myoclonus, ataxia, and myopathy. We describe a novel homoplasmic m.7484A>G mutation in the tRNASer(UCN) gene affecting the third base of the anticodon triplet in a girl with profound intellectual disability, spastic tetraplegia, sensorineural hearing loss, a clinical history of epilepsia partialis continua and vomiting, typical of MELAS syndrome, leading to a myoclonic epilepticus status, and myopathy with severe COX deficiency at muscle biopsy. The mutation was also found in the homoplasmic condition in the mother who presented with mild cognitive deficit, cerebellar ataxia, myoclonic epilepsy, sensorineural hearing loss and myopathy with COX deficient ragged-red fibers consistent with MERRF syndrome. This is the first anticodon mutation in the tRNASer(UCN) and the second homoplasmic mutation in the anticodon triplet reported to date.
We report the second case, to the best of our knowledge, of a mother with Prader–Willi syndrome (PWS) who gave birth to a daughter with Angelman syndrome (AS). The menarche occurred when she was 16, ...and the following menstrual cycles were irregular, but she never took sexual hormone replacement therapy. At the age of 26, our patient with PWS became pregnant. The diagnosis was confirmed by molecular genetic testing that revealed a ~5.7 Mb deletion in the 15q11.1–15q13 region on the paternal allele in the mother with PWS and the maternal one in the daughter with AS, respectively. Both the mother with PWS and the daughter with AS showed peculiar clinical and genetic features of the two syndromes. Our case report reaffirms the possible fertility in PWS; therefore, it is very important to develop appropriate socio-sexual education programs and fertility assessments in order to guarantee the expression of a healthy sexuality.
Methyl-CpG-binding protein 2 (MeCP2) is a nuclear protein highly expressed in neurons that is involved in transcriptional modulation and chromatin remodeling. Mutations in MECP2 in females are ...associated with Rett syndrome, a neurological disorder characterized by a normal neonatal period, followed by the arrest of development and regression of acquired skills. Although it was initially thought that MECP2 pathogenic mutations in males were not compatible with life, starting from 1999 about 60 male patients have been identified and their phenotype varies from severe neonatal encephalopathy to mild intellectual disability. Targeted next-generation sequencing of a panel of intellectual disability related genes was performed on two unrelated male patients, and two missense variants in MECP2 were identified (p.Gly185Val and p.Arg167Trp). These variants lie outside the canonical methyl-CpG-binding domain and transcription repression domain domains, where the pathogenicity of missense variants is more difficult to establish. In both families, variants were found in all affected siblings and were inherited from the asymptomatic mother, showing skewed X-chromosome inactivation. We report here the first missense variant located in AT-hook domain 1 and we underline the importance of MECP2 substitutions outside the canonical MeCP2 domains in X-linked intellectual disability.
Expression of miR-132 in Down syndrome subjects Salemi, Michele; Barone, Concetta; Salluzzo, Maria Grazia ...
Human cell : official journal of Human Cell Research Society,
07/2018, Letnik:
31, Številka:
3
Journal Article
Interstitial deletions of the long arm of chromosome 12 are rare, with a dozen patients carrying a deletion in 12q21 being reported. Recently a critical region (CR) has been delimited and could be ...responsible for the more commonly described clinical features, such as developmental delay/intellectual disability, congenital genitourinary and brain malformations. Other, less frequent, clinical signs do not seem to be correlated to the proposed CR. We present seven new patients harboring non-recurrent deletions ranging from 1 to 18.5 Mb differentially scattered across 12q21. Alongside more common clinical signs, some patients have rarer features such as heart defects, hearing loss, hypotonia and dysmorphisms. The correlation of haploinsufficiency of genes outside the CR to specific signs contributes to our knowledge of the effect of the deletion of this gene-poor region of chromosome 12q. This work underlines the still important role of copy number variations in the diagnostic setting of syndromic patients and the positive reflection on management and family genetic counseling.
After the global spread of SARS-CoV-2, research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. ...However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness remains uncertain.
In this context, this study aims at quantifying the proportion of SARS-CoV-2 antibody seroprevalence, studying the changes in antibody levels over time, and analyzing the association between the biochemically verified smoking status and SARS-CoV-2 infection.
The research design involves a 6-month prospective cohort study with a serial sampling of the same individuals. Each participant will be surveyed about their demographics and COVID-19-related information, and blood sampling will be collected upon recruitment and at specified follow-up time points (ie, after 8 and 24 weeks). Blood samples will be screened for the presence of SARS-CoV-2-specific antibodies and serum cotinine, being the latter of the principal metabolite of nicotine, which will be used to assess participants' smoking status.
The study is ongoing. It aims to find a higher antibody prevalence in individuals at high risk for viral exposure (ie, health care personnel) and to refine current estimates on the association between smoking status and SARS-CoV-2/COVID-19.
The added value of this research is that the current smoking status of the population to be studied will be biochemically verified to avoid the bias associated with self-reported smoking status. As such, the results from this survey may provide an actionable metric to study the role of smoking in SARS-CoV-2 infection and COVID-19 outcomes, and therefore to implement the most appropriate public health measures to control the pandemic. Results may also serve as a reference for future clinical research, and the methodology could be exploited in public health sectors and policies.
DERR1-10.2196/32285.
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