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G Neri

Publications and source records attributed to G Neri.

At least 37 records · Page 2Linked to original sources
PubMed2003

PTPN11 mutations are not responsible for the Cardiofaciocutaneous (CFC) syndrome.

Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomalies/mental retardation syndrome characterized by congenital heart defects, characteristic facial appearance, short stature, ectodermal abnormalities and mental retardation. It was described in 1986, and to date is of unknown genetic etiology. All reported cases are sporadic, born to non-consanguineous parents and have apparently normal chromosomes. Noonan and Costello syndromes remain its main differential diagnosis. The recent finding of PTPN11 missense mutations in 45-50% of the Noonan patients studied with penetrance of almost 100% and the fact that in animals mutations of this gene cause defects of semilunar valvulogenesis, made PTPN11 mutation screening in CFC patients a matter of interest. We sequenced the entire coding region of the PTPN11 gene in ten well-characterised CFC patients and found no base changes. We also studied PTPN11 cDNA in our patients and demonstrated that there are no interstitial deletions either. The genetic cause of CFC syndrome remains unknown, and PTPN11 can be reasonably excluded as a candidate gene for the CFC syndrome, which we regard as molecular evidence that CFC and Noonan syndromes are distinct genetic entities.

Abnormalities, Multiple↗
PubMed2003

Effect of biventricular pacing on metabolism and perfusion in patients affected by dilated cardiomyopathy and left bundle branch block: evaluation by positron emission tomography.

AIMS: Evaluate the possible changes in myocardial metabolism and perfusion induced by biventricular pacing (BIVP) in patients affected by dilated cardiomyopathy (DC) and left bundle branch block (LBBB). METHODS AND RESULTS: Eight male patients (aged 60-79 years, mean 69) affected by DC (NYHA functional class III and ejection fraction <40%) were submitted to cardiac PET in basal condition and 3 weeks after the implantation of a biventricular device. Metabolism was evaluated using F18-fluorodeoxyglucose (FDG), by the glucose load-insulin technique, and perfusion by N13-ammonia (NH3), injected at rest. Visual and a semi quantitative analyses were performed, calculating by ROIs the septum to lateral uptake ratio (SLR). The myocardial blood flow (MBF) was also calculated in ml/min/g using a dynamic acquisition and a modified Patlak method. In all 8 patients a selective defect in FDG uptake in the septum was present in basal condition (mean SLR 0.59+/-0.17) with a 'reverse mismatch' effect with respect to NH3 (mean SLR 1.07+/-0.18). During BIVP the distribution of FDG in the septal area significatively improved (mean SLR 0.86+/-0.15 P=0.011 with respect to basal); on the contrary, no significant changes were found in NH3 uptake (mean SLR 1.02+/-0.23, P=ns). On quantitative analysis the mean MBF in the septum was 1.05+/-0.37 in basal condition and did not significantly change during BIVP (0.95+/-0.34, P=0.06). CONCLUSIONS: Our results suggest that, in patients affected by DC and LBBB, BIVP improves the septal glucose metabolism without significant changes in myocardial perfusion.

Aged↗
PubMed2003

Reactivation of silenced genes and transcriptional therapy.

The purpose of this review is to discuss the potential role of "transcriptional therapy" to modulate the expression of target genes in order to treat monogenic as well as multifactorial disorders. In vitro and in vivo experiments with DNA demethylating and histone hyperacetylating drugs are currently performed in several laboratories on a variety of genes. In attempting to place these results into perspective, we divided the target genes into four major categories: (1) single genes with a hypermethylated CpG island; (2) single genes without a CpG island; (3) groups of genes silenced by aberrant DNA methylation; and (4) groups of genes silenced by lack of histone acetylation. We discuss the latest advances in the field of chromatin regulation and, in particular, the role of histone methylation and that of RNA interference in gene silencing. We can expect that in the future regulation of transcription will become an effective treatment for several genetic conditions.

Acetylation↗
PubMed2003

Continuing validity of pectoralis major muscle flap 25 years after its first application.

Surgical treatment of malignant cervico-facial tumours often includes vast demolition of mucosal, cutaneous, muscle and bone tissues, requiring immediate repair of the extensive loss of substance with reconstructive pedicled or revascularised free flaps. Still today, when it is not necessary to reconstruct the mandibular bone or in particular clinical situations as found in patients in whom microsurgery is contraindicated due to general conditions or in those cases of unsuccessful microsurgical flaps, use of the pedicled flaps is still indicated, particularly the myocutaneous flap of the major pectoral muscle described approximately 25 years ago, and quite rightly referred to as "work horse" or "spare wheel" of reconstructive surgery. Study population comprises 33 patients (27 male, 6 female, mean age: 61 years, range: 36-86) observed between 2000-2002. These patients were submitted to demolitive surgery on account of malignant cervico-facial neoplasias. The role of the major pectoral muscle pedicled flap is emphasised stressing that resection of the pedicle, even a few weeks after transplant, together with the subclavicular passage, may avoid the majority of the well-known functional and aesthetic problems related to this reparative technique.

Adult↗
PubMed2002

Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.

McKusick-Kaufman syndrome comprises hydrometrocolpos, polydactyly, and congenital heart defects and overlaps with Bardet-Biedl syndrome, comprising retinitis pigmentosa, polydactyly, obesity, mental retardation, and renal and genital anomalies. Bardet-Biedl syndrome is genetically heterogeneous with three cloned genes ( BBS2, BBS4, and MKKS) and at least three other known loci ( BBS1, BBS3, and BBS5). Both McKusick-Kaufman syndrome and Bardet-Biedl syndrome are inherited in an autosomal recessive pattern, and both syndromes are caused by mutations in the MKKS gene. However, mutations in MKKS are found in only 4%-11% of unselected Bardet-Biedl syndrome patients. We hypothesized that an analysis of patients with atypical Bardet-Biedl syndrome and McKusick-Kaufman syndrome (Group I; 15 probands) and patients with Bardet-Biedl syndrome who had linkage results inconsistent with linkage to the other loci (Group II; 12 probands) could increase the MKKS mutation yield. Both mutant alleles were identified in only two families in Group II. Single (heterozygous) sequence variations were found in three Group I families and in two Group II families. Combining these results with previously published data showed that only one mutant allele was detected in nearly half of all patients screened to date, suggesting that unusual mutational mechanisms or patterns of inheritance may be involved. However, sequencing of the BBS2 gene in these patients did not provide any evidence of digenic or "triallelic" inheritance. The frequency of detected mutations in MKKS in Group II patients was 24%, i.e., six times higher than the published rate for unselected BBS patients, suggesting that small-scale linkage analyses may be useful in suitable families.

Abnormalities, Multiple↗
PubMed2002

Blood lead reference values: the results of an Italian polycentric study.

This paper presents the results of a polycentric study carried out in seven different areas, organized by the Italian Society of Reference Values (SIVR) for assessing reference values of lead in blood (B-Pb) at the current doses of the metal to general population. The estimated arithmetic mean for B-Pb in males was of 45.1 microg/l and 30.6 microg/l in females; the 95th centile was 100 and 60 for males and females, respectively. The main variables influencing B-Pb levels were gender, age, BMI, outside sport practice, alcohol consumption and smoking habits, while the geographic area and the urban residence did not affect the metal concentration in blood.

Adolescent↗
PubMed2002

[Rhinocerebral mucormycosis: report of a rare case in the head-neck and chest area].

Mucormycosis is a severe fungal disease. It can present in two clinical forms: localized or disseminated. The most common, often lethal, form is localized rhinocerebral mucormycosis and is associated with diabetes, debilitation and immunologic deficiencies. The primary location is generally found in the nasal cavity, paranasal sinuses or hard palate. The infective process can extend into the orbita, the cavernosus sinus, the pterygium-palatine and infratemporal fossae with generation of mycotic emboli that can plug the cerebral arteries and, in certain circumstances, can lead to death if it goes untreated. This work describes a clinical case of a 76-years-old patient with a previous history of alcoholism and glucose intolerance, affected by rhinocerebral mucormycosis with extension to the lungs. A general medicine division sent the patient for observation by a specialist since, at the time of hospitalization, objective testing showed signs of an ulcerating lesion of the alveolar edge of the left hemipalate associated with a bilateral pulmonary neoformation suspected to be neoplastic. The patient underwent pulmonary and maxillo-facial surgical resection and medical therapy. The authors discuss the appropriateness of diagnosis and treatment procedures in cases of mucormycosis in association with other pathologies, that can complicate the clinical picture, delaying diagnosis and treatment. The authors point out the need to perform in a short time an adequate medical and surgical treatment of mucormycosis, because of the risk of intracranial extension, leading to an increased mortality, even as high as 80%. The longer it takes to reach a diagnosis the more radical the surgical treatment will need to be.

Aged↗
PubMed2001

p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.

p63 mutations have been associated with EEC syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip/palate), as well as with nonsyndromic split hand-split foot malformation (SHFM). We performed p63 mutation analysis in a sample of 43 individuals and families affected with EEC syndrome, in 35 individuals affected with SHFM, and in three families with the EEC-like condition limb-mammary syndrome (LMS), which is characterized by ectrodactyly, cleft palate, and mammary-gland abnormalities. The results differed for these three conditions. p63 gene mutations were detected in almost all (40/43) individuals affected with EEC syndrome. Apart from a frameshift mutation in exon 13, all other EEC mutations were missense, predominantly involving codons 204, 227, 279, 280, and 304. In contrast, p63 mutations were detected in only a small proportion (4/35) of patients with isolated SHFM. p63 mutations in SHFM included three novel mutations: a missense mutation (K193E), a nonsense mutation (Q634X), and a mutation in the 3' splice site for exon 5. The fourth SHFM mutation (R280H) in this series was also found in a patient with classical EEC syndrome, suggesting partial overlap between the EEC and SHFM mutational spectra. The original family with LMS (van Bokhoven et al. 1999) had no detectable p63 mutation, although it clearly localizes to the p63 locus in 3q27. In two other small kindreds affected with LMS, frameshift mutations were detected in exons 13 and 14, respectively. The combined data show that p63 is the major gene for EEC syndrome, and that it makes a modest contribution to SHFM. There appears to be a genotype-phenotype correlation, in that there is a specific pattern of missense mutations in EEC syndrome that are not generally found in SHFM or LMS.

Alternative Splicing↗
PubMed2001

New syndrome of mental retardation, Robin sequence, and brachydactyly.

We report on two sibs, brother and sister, affected with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome, characterized by mild to moderate psychomotor delay, Robin sequence, peculiar facial appearance, and brachydactyly. To our knowledge, this combination of anomalies has not been reported previously. The occurrence of a similar pattern of anomalies in brother and sister suggests autosomal recessive inheritance; however, dominant transmission with reduced penetrance cannot be ruled out in our patients, since minor clinical signs, such as brachydactyly, are also present in the father.

Abnormalities, Multiple↗
PubMed2001

CDKN2A germline splicing mutation affecting both p16(ink4) and p14(arf) RNA processing in a melanoma/neurofibroma kindred.

The CDKN2A locus encodes two tumor suppressor proteins, p16(ink4) and p14(arf), through use of alternative first exons. CDKN2A mutations detected in melanoma families are usually missense or nonsense changes which mainly impair p16(ink4) function. Large genomic deletions spanning the entire locus have been observed in two pedigrees with melanomas and nervous tumors. We have detected a novel splice site mutation in a family with melanomas, neurofibromas, and multiple dysplastic nevi. Both alternative mRNAs produced by the mutant allele lacked shared sequences from exon 2, which encodes a substantial portion (>50%) of both p16(ink4) and p14(arf) proteins. The development of neurofibromas can be explained by cooperative effects of combined inactivation of p16(ink4) and p14(arf) or, alternatively, of p14(arf) alone.

Adolescent↗
PubMed2001

Proadrenomedullin N-terminal 20 peptide (PAMP) enhances proliferation of rat zona glomerulosa cells by activating MAPK cascade.

The effect of proadrenomedullin N-terminal 20 peptide (PAMP) on the proliferative activity of rat zona glomerulosa (ZG) cells has been investigated. Dispersed rat ZG cells were cultured in vitro for 24 h and then exposed to PAMP for an additional 24 h, and the proliferation rate was assessed by the 5-bromo-2'-deoxyuridine (BrdU) incorporation technique. PAMP dose-dependently increased the percentage of BrdU-positive cells, with a maximal effective concentration observed at 10(-8) M. The tyrosine kinase (TK) inhibitor, tyrphostin-23, and the p42/p44 MAPK inhibitor, PD-98059, abolished the proliferogenic effect of PAMP, while the protein kinase (PK) A inhibitor, H-89, and the PKC inhibitor, calphostin-C, were ineffective in blocking the response to PAMP. PAMP (10(-8) M) enhanced TK and MAPK activity of dispersed rat ZG cells. The stimulatory action of PAMP on TK activity was annulled by tyrphostin-23, while that on MAPK activity was abolished by either tyrphostin-23 or PD-98059. Taken together, these data indicate that PAMP enhances proliferation of cultured rat ZG cells, through the TK-dependent activation of p42/p44 MAPK cascade.

Adrenomedullin↗
PubMed2001

Familial microsatellite-stable non-polyposis colorectal cancer: incidence and characteristics in a clinic-based population.

BACKGROUND: About 15%-20% of colorectal cancers (CRCs) are familial. While a fraction of these arise in the context of hereditary syndromes, the causes underlying the majority of familial CRCs are not yet understood. PATIENTS AND METHODS: Family history of cancer, clinical characteristics, and microsatellite instability (MSI) in a series of 100 consecutive CRC patients were evaluated. RESULTS: Eighteen patients had a positive family history of CRC in a first-degree relative. Of these, two had a clinical diagnosis of familial adenomatous polyposis (FAP), and three were diagnosed with hereditary non-polyposis colorectal cancer (HNPCC) following results of MSI analysis. A diagnosis of HNPCC was also established in a fourth patient with early onset CRC, who had a second-degree relative with CRC, and whose tumor was positive for MSI. The remaining 13 familial CRCs did not show MSI in tumor DNA. The mean age at tumor diagnosis in patients with familial microsatellite-stable (MSS) CRC was higher than in HNPCC and FAP patients and similar to that recorded in sporadic cases. The incidence of second primary malignancies was significantly higher in familial MSS CRC probands (n = 4) compared to patients who did not have a diagnosis of FAP or HNPCC and did not have first-degree relatives affected with CRC (n = 6, in a total of 81 probands with these characteristics). CONCLUSIONS: These results define the existence of a subset of familial CRCs characterized by relatively late age at onset, high incidence of second primary tumors, and absence of MSI in tumor DNA.

Adenomatous Polyposis Coli↗
PubMed2001

Mutations of the 'minor' mismatch repair gene MSH6 in typical and atypical hereditary nonpolyposis colorectal cancer.

Mutations of the mismatch repair (MMR) genes MLH1 and MSH2 are associated with hereditary nonpolyposis colorectal cancer (HNPCC), a highly penetrant autosomal dominant condition characterized by hypermutability of short tandemly repeated sequences in tumor DNA. Mutations of another MMR gene, MSH6, seem to be less common than MLH1 and MSH2 defects, and have been mostly observed in atypical HNPCC families, characterized by a weaker tumor family history, higher age at disease onset, and low degrees of microsatellite instability (MSI), predominantly involving mononucleotide runs. We have investigated the MSH6 gene sequence in the peripheral blood of 4 HNPCC and 20 atypical HNPCC probands. Two frameshift mutations within exon 4 were detected in 2 patients. One mutation was found in a proband from a typical HNPCC family, who had developed a colorectal cancer (CRC), a gastric cancer and a rectal adenoma. The CRC and the adenoma showed mild MSI limited to mononucleotide tracts, while the gastric carcinoma was microsatellite stable. The other mutation was detected in an atypical HNPCC proband, whose CRC showed widespread MSI involving both mono- and dinucleotide repeats. The phenotypic variability associated with MSH6 constitutional mutations represents a complicating factor for the optimization of strategies aimed at identifying candidates to MSH6 genetic testing.

Adult↗