Mattia Gentile

Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas

Biallelic germline mutations in the base excision repair gene MYH have been reported in patients with multiple colorectal adenomas and cancer and in sporadic FAP patients not showing a detectable APC germline mutation. In this study, the prevalence of the common Y165C and G382D germline variants of the MYH gene was examined in 70 FAP/AAPC patients with no detectable APC mutation and a family history compatible with recessive inheritance. In addition, 141 normal‐population adenoma patients (mean number of adenomas, 2.8; range, 1–9) and 52 clean colon controls were studied. The entire coding region of the MYH gene was analyzed in Y165C or G382D heterozygous patients. Since the same second mutational event (a 3 bp deletion in exon 14, 1395delGGA) was detected in 3 patients, the prevalence of this variant was also examined in all groups. In all, 14 of 70 patients in the FAP/AAPC group (20%; 95% CI = 11.7–31.6%) had biallelic germline MYH variants and 3 were heterozygotes (4.3%). None of the 141 normal‐population adenoma patients carried biallelic germline MYH variants (95% CI = 0.06–4.1%) and 3 were heterozygotes (2.1%). In the control group, no MYH variants were detected. These results indicated that MYH‐associated polyposis (MAP) is present in about 20% of Italian FAP/AAPC patients, in whom no germline APC mutation is detectable and showing a family history compatible with recessive inheritance, and in a small fraction of patients with colorectal adenomas in the general population. In addition, our data suggest that mutation 1395delGGA is a subpolymorphic MYH mutational event in some Caucasian populations.

Sex chromosome loss, micronuclei, sister chromatid exchange and aging: a study including 16 centenarians

In the present study we analysed the possible effect of age, sex and smoking on the mean values of micronucleus (MN) and sister chromatid exchange (SCE) frequencies on peripheral blood obtained from 38 subjects ranging in age from 16 to 63 years and 16 centenarians. The mean number of binucleated cells with micronuclei varied in function of age and sex (as demonstrated by the analysis of covariance (F=13.13; P<0.001), particularly evident was the increment observed in women with increasing age (interaction age/sex: F=5.53; P<0.05). Smoking habits had no effects on MN frequency (F=0.36; P>0.05). Sex (F=4.18; P<0.05) and smoking habits (F=14.64; P<0.001) influenced significantly SCE per cell frequencies, but age had no effects on them (F=2.45; P>0.05). The age-associated increase of sex chromosome loss was studied using fluorescence in situ hybridisation (FISH) on interphase nuclei. The loss of Y signals was observed in approximately 10% of interphase cells from the centenarians males, that is six times more often than in the younger control men (approximately 1.6%). The frequency of X signal loss (approximately 1.7%) in young women was similar to that observed in male controls of the same age but the incidence of the X chromosome aneuploidy in centenarian females was appreciably higher (approximately 22%) than that found for the Y chromosome in males. These results were correlated with the data on MN formation and a positive correlation between the percentage of aneuploid cells (FISH) and MN values was observed (r=0.50; P<0.05).

Characteristics, associations and outcome of absent pulmonary valve syndrome in the fetus

To assess in a population of 21 fetuses diagnosed with absent pulmonary valve syndrome (APVS) the accuracy of prenatal diagnosis, the incidence of extracardiac and chromosomal anomalies and the perinatal outcome.

Novel application of 4D sonography with B-flow imaging and spatio-temporal image correlation (STIC) in the assessment of the anatomy of pulmonary arteries in fetuses with pulmonary atresia and ventricular septal defect

To assess the reliability of two‐dimensional gray‐scale (2D) and color Doppler echocardiography in the study of the size and anatomy of the central pulmonary arteries and of the sources of pulmonary blood flow in a case series of fetuses with pulmonary atresia and ventricular septal defect (PA‐VSD), and to evaluate whether the use of 4D ultrasound with B‐flow imaging and spatio‐temporal image correlation (STIC) can improve prenatal diagnostic accuracy.

Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases

Objective: To assess the accuracy of prenatal diagnosis, the incidence of extracardiac and chromosomal anomalies, and the perinatal outcome in a population of fetuses with common arterial trunk (CAT). Design: Observational study of 23 fetuses from three referral centres with a confirmed diagnosis of CAT. All underwent fetal echocardiography, detailed anatomical scanning, and karyotyping. In 19 cases, FISH analysis was done to detect 22q11 microdeletion. The following variables were evaluated: gestational age at diagnosis, anatomical variants of the CAT, presence of extracardiac and chromosomal anomalies, pregnancy, and fetal–neonatal outcome. Necropsy reports and postnatal files were available for confirmation of the prenatal diagnosis in all cases. Results: The prenatal diagnosis proved correct in 23 of 24 cases, the last being pulmonary atresia with ventricular septal defect (PAVSD). A second cardiovascular anomaly was present in eight cases (34.8%); extracardiac anomalies were found in 10 (43.4%). FISH analysis showed 22q11 microdeletion in six of 19 cases (31.6%). Outcomes were as follows: eight terminations of pregnancy (34.8%), two intrauterine deaths (8.7%), five postnatal deaths (before or after surgery) (21.7%); the remaining eight neonates (34.8%) are alive and thriving after surgery (six) or awaiting surgery (two). Conclusions: CAT can be reliably diagnosed and characterised in prenatal life, although differentiation from PAVSD may be challenging. The association with chromosomal anomalies is consistent (8.7%), but there is a higher risk of 22q11 microdeletion (31.6%), in agreement with postnatal studies. The relatively poor survival rate (34.8%) reflects the high rate of terminations and the unfavourable cardiac anatomy in some cases.

Detection of the Emerging Rotavirus G9 Serotype at High Frequency in Italy

ABSTRACT Group A human rotavirus strains belonging to the unusual serotype G9 were detected at high frequency in stool specimens from infected children with acute diarrhea in Bari, Italy, during a 15-month survey from March 2001 to June 2002. This may signify a local reemergence of the G9 rotaviruses detected in Italy in the early and mid-1990s or may be related to the global emergence of G9 rotaviruses in recent years.

FISH and cytogenetic characterization of a terminal chromosome 1q deletion: Clinical case report and phenotypic implications

We report a 24‐year‐old woman with minor facial anomalies, mental retardation, seizures, and partial agenesis of the corpus callosum. Cytogenetic analysis showed a de novo terminal chromosome 1 long arm deletion. FISH with a panel of chromosome 1q42‐qter bands‐specific BAC and YAC clones located the breakpoint at the 1q42‐q43 junction, with monosomy restricted to the 1q43 and 1q44 bands. The changing craniofacial phenotype of this patient with age is described as part of the del(1)(q) syndrome natural history. The patients features are compared with those of other patients with similar deletions, and variable phenotypic findings due to different deleted chromosomal segments are discussed.

Two- and four-dimensional echocardiography with B-flow imaging and spatiotemporal image correlation in prenatal diagnosis of isolated total anomalous pulmonary venous connection.

To explore whether the use of four dimensional (4D) ultrasound examination with B‐flow imaging and spatiotemporal image correlation (STIC) can supply additional information with respect to two‐dimensional (2D) gray‐scale and color Doppler echocardiography in the prenatal characterization of isolated total anomalous pulmonary venous connection (TAPVC).

An unusual dicentric Y chromosome with a functional centromere with no detectable alpha-satellite

We describe an unusual marker chromosome Y. This marker is present in 5% of the lymphocytes of a dysgenetic woman showing a mosaic karyotype 45,X/46,XY/ 47,XY+mar. Q-banding revealed that the marker was morphologically identical to the Y chromosome of the patient but presented the primary constriction in the heterochromatic region. C-banding confirmed that the heterochromatic region was C-positive; furthermore, it showed two spots in the euchromatic region in a position corresponding to that of the centromere in the normal Y Fluorescence in situ hybridization with the centromere-specific probe pDP 97 and the pancentromeric alpha-satellite probe α27α30 failed to detect any signal at the primary constriction site. To improve the characterization of the marker chromosome, hybridization was performed using pDP 105, a probe located on the short arm of the Y chromosome, together with chromosome-Y- specific paint-hybridizing to the single sequence spanning the Y short arm. In both cases, positive signals telomeric to the inactive centromere were observed. Possible mechanisms resulting in the formation of the marker chromosome are discussed.

COACH syndrome: Report of two brothers with congenital hepatic fibrosis, cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation

Congenital hepatic fibrosis (CHF) is probably the most common cause of non-icteric hepatosplenomegaly and is encountered mainly in children and young adults. We describe here two brothers from healthy, non-consanguineous parents. The patients showed early hepatosplenomegaly, portal hypertension, and no apparent kidney involvement. Clinical and laboratory findings were similar in both patients. Liver biopsies showed the presence of broad septa of fibrous tissue containing abundant bile ducts, portal tracts enlarged by fibrosis, and preserved lobular architecture. The histological findings were suggestive of CHF. Ophthalmological assessment demonstrated visual impairment with mild exotropia, nystagmus, and oculomotor apraxia. Neurological examination showed moderate mental retardation and cerebellar ataxia. Brain MRI confirmed cerebellar malformation with inferior vermis hypoplasia. This pattern of defects is consistent with COACH syndrome (Cerebellar vermis hypoplasia, Oligophrenia, congenital Ataxia, Coloboma, Hepatic fibrocirrhosis) which has previously been reported in five other cases. Our report may contribute to a better delineation of the COACH syndrome phenotype in the spectrum of oculo-encephalohepato-renal disorders.