Search PubMed⌕ Search

Biomedical subjects

B Dallapiccola

Publications and source records attributed to B Dallapiccola.

At least 19 recordsLinked to original sources
PubMed2005

Quantitative ultrasound of the hand phalanges in a cohort of monozygotic twins: influence of genetic and environmental factors.

OBJECTIVE: Our objective was to evaluate the similarities and differences in bone mass and structure between pairs of monozygotic twins as measured by means of the quantitative ultrasound (QUS) technique. DESIGN: A cohort of monozygotic twins was measured by QUS of the hand phalanges using the DBM sonic bone profiler (IGEA, Carpi, Italy). The parameters studied were amplitude-dependent speed of sound (AD-SoS), ultrasound bone profile index (UBPI), signal dynamics (SDy) and bone transmission time (BTT). Linear correlation coefficients, multivariate linear analysis and the ANOVA test were used to assess intrapair associations between variables and to determine which factors influence the intrapair differences in QUS variables. PATIENTS: One hundred and six pairs of monozygotic twins were enrolled in the study, 68 females and 38 males in the age range 5 to 71 years. RESULTS: Significant intrapair correlations were obtained in the whole population and separately for males and females, regarding height ( r =0.98-0.99, p <0.0001), weight ( r =0.95-0.96, p <0.0001), AD-SoS ( r =0.90-0.92, p <0.0001), BTT ( r =0.94-0.95, p <0.0001) and other QUS parameters ( r >0.74, p <0.0001). Multivariate analysis revealed that intrapair differences between AD-SoS, SDy, UBPI and BTT are significantly influenced by age in the whole population and in the female population. Furthermore, the ANOVA test showed, for the female group, a significant increase in the intrapair differences in SDy and UBPI above 40 years. CONCLUSIONS: A relative contribution of genetic factors to skeletal status could be observed by phalangeal QUS measurement in monozygotic twins. A significant increase in the intrapair difference in QUS parameters with increasing age and onset of menopause also suggests the importance of environmental factors in the female twin population.

Adolescent↗
PubMed2005

Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions.

OBJECTIVE: To develop and compare two new technologies for diagnosing a contiguous gene syndrome, the Williams-Beuren syndrome (WBS). METHODS: The first proposed method, named paralogous sequence quantification (PSQ), is based on the use of paralogous sequences located on different chromosomes and quantification of specific mismatches present at these loci using pyrosequencing technology. The second exploits quantitative real time polymerase chain reaction (QPCR) to assess the relative quantity of an analysed locus. RESULTS: A correct and unambiguous diagnosis was obtained for 100% of the analysed samples with either technique (n = 165 and n = 155, respectively). These methods allowed the identification of two patients with atypical deletions in a cohort of 182 WBS patients. Both patients presented with mild facial anomalies, mild mental retardation with impaired visuospatial cognition, supravalvar aortic stenosis, and normal growth indices. These observations are consistent with the involvement of GTF2IRD1 or GTF2I in some of the WBS facial features. CONCLUSIONS: Both PSQ and QPCR are robust, easy to interpret, and simple to set up. They represent a competitive alternative for the diagnosis of segmental aneuploidies in clinical laboratories. They have advantages over fluorescence in situ hybridisation or microsatellites/SNP genotyping for detecting short segmental aneuploidies as the former is costly and labour intensive while the latter depends on the informativeness of the polymorphisms.

Aneuploidy↗
PubMed2005

The PINK1 phenotype can be indistinguishable from idiopathic Parkinson disease.

Mutations in the PINK1 gene cause autosomal recessive parkinsonism characterized by early onset and a variable phenotypic presentation. A patient homozygous for the Ala168Pro mutation has been fully characterized clinically. Apart from onset at age 39 years and the excellent and sustained response to levodopa, all clinical and laboratory features, including SPECT and assessment of autonomic function, were indistinguishable from typical idiopathic Parkinson disease.

Age of Onset↗
PubMed2005

The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive disorder caused by mutations in the PANK2 gene. The authors report clinical and genetic findings of 16 patients with PKAN. The authors identified 12 mutations in the PANK2 gene, five of which were new. Only nine patients could be classified as classic or atypical PKAN, and intermediate phenotypes are described. Two patients presented with motor tics and obsessive-compulsive behavior suggestive of Tourette syndrome.

Adolescent↗
PubMed2005

The epsilon-sarcoglycan gene in myoclonic syndromes.

Mutations in the epsilon-sarcoglycan gene (SGCE) are associated with familial myoclonus dystonia, but the full spectrum of the phenotype may not be fully defined. We screened 58 individuals with a range of myoclonic/dystonic syndromes for SGCE mutations. We found mutations (three of them novel) in six (21%) of the 29 patients with essential myoclonus and myoclonic dystonia, but did not find mutations in the 29 patients with other phenotypes.

Age of Onset↗
PubMed2005

LGI1 gene mutation screening in sporadic partial epilepsy with auditory features.

Partial epilepsy with auditory features occasionally segregates in families as an autosomal dominant trait. In some families mutations in the leucine-rich glioma inactivated (LGI1) gene have been identified. Sporadic cases might harbour either denovo or low-penetrant LGI1 mutations, which will substantially alter the family risk for epilepsy. We selected sixteen sporadic patients with cryptogenic temporal lobe epilepsy and partial seizures with auditory features. We compared clinical features of these patients with those of published autosomal dominant family cases. We screened these patients for LGI1 mutations. Comparing the sporadic patients with the published familial cases no difference in either the primary auditory features or in the other associated epileptic manifestations was identified. Sequence analysis of the whole LGI1 gene coding regions in sporadic patients did not reveal changes in the LGI1 gene. The genetic analysis demonstrates that LGI1 is not a major gene for sporadic cases of partial epilepsy with auditory features at least in the Italian population. Screening of sporadic patients for LGI1 mutations appears not useful in genetic counselling of these patients.

Adult↗
PubMed2005

Pure trisomy 19p syndrome in an infant with an extra ring chromosome.

We report a 12-month-old infant evaluated for severe hypotonia, psychomotor retardation, and facial dysmorphisms, including round face, high prominent forehead, downward slanted palpebral fissures, hypertelorism, short nose, chubby cheeks, long philtrum, anteverted lower lip, low-set asymmetric and dysmorphic ears. Karyotype analysis disclosed an extra mosaic ring chromosome, which included the whole 19p arm. Four additional patients with supernumerary ring 19 chromosomes have been reported, but none of them had pure trisomy 19p.

Chromosome Banding↗
PubMed2004

Clinical and genetic studies in hereditary spastic paraplegia with thin corpus callosum.

BACKGROUND: A complicated form of recessive hereditary spastic paraplegias (HSPs) with thin corpus callosum (TCC) was first described in Japan, and most of the Japanese families showed linkage to chromosome 15q13-15. A recessive HSP locus (SPG11) has also been mapped to chromosome 15q13-15 in Italian and North American families with and without TCC, and it overlaps the region identified in the Japanese families. OBJECTIVE: To study clinically and genetically 12 Italian families with HSP and TCC. METHODS: The authors investigated 18 affected and 30 healthy individuals from 12 unrelated Italian families with recessive HSP-TCC. Clinical, neurophysiologic, and neuroradiologic studies were undertaken. All patients were negative for SPG7 mutations. Genetic linkage analyses were carried out with polymorphic DNA markers on 15q13-15. RESULTS: Five families were consistent with linkage, thus defining a 19.8-cM region between markers D15S1007 and D15S978, encompassing the SPG11 interval. In one consanguineous family, linkage could be firmly excluded, confirming genetic heterogeneity. Two families appeared not linked to the region, but this could not be firmly proved because of the small family size. The remaining four families were uninformative for linkage purposes. CONCLUSION: HSP-TCC is common in Italy. The phenotype is fairly homogeneous and is associated with impaired cognition. There are at least two loci for HSP-TCC, one of which is on chromosome 15q13-15.

Adolescent↗
PubMed2004

Evaluation of a DHPLC-based assay for rapid detection of RET germline mutations in Italian patients with medullary thyroid carcinoma.

Causative gain-of-function mutations of the RET tyrosine-kinase receptor gene have been reported in more than 95% of inherited cases of medullary thyroid carcinoma (MTC; OMIM# 155240). Most RET activating mutations are clustered in mutational "hot spots" in exons 10, 11, 13, 14, 15 and 16 and are usually detected by single-strand conformation polymorphism (SSCP) followed by direct sequencing. To improve sensitivity, time and costs of mutational screening we have developed a denaturing high performance chromatography (DHPLC) protocol, based on the detection of heteroduplex molecules by ion-pair reverse-phase liquid chromatography under partially denaturing conditions. The mutational screening of RET exons 10, 11, 13-16 was performed in a total of 111 subjects, including 45 MTC patients and 49 relatives with known RET mutations and 17 individuals, being at risk of hereditary MTC and carrying unknown RET alleles. Heteroduplex peaks with a distinct and reproducible DHPLC elution profile allowed the detection of both rare and common RET mutations. Overall, the DHPLC-based methodology showed a high level of sensitivity and accuracy, nearing 100%. Furthermore, our protocol showed the ability to identify: 1) all the mutated codons of RET located in the "hot spots" domain; 2) the different point mutations occurring in the same codon of RET gene; 3) less frequent or rare mutations; 4) polymorphisms. As such, it can be proposed as a relatively simple and highly accurate method for a rapid genetic testing for members of MTC families.

Carcinoma, Medullary↗
PubMed2004

Preliminary data suggest that mutations in the CgRP pathway are not involved in human sporadic cryptorchidism.

In testicular descent to the scrotum, a multistep process, many anatomical and hormonal factors play a role. Cryptorchidism occurs in about 1-2% of males and may cause secondary degeneration of the testes. Animal models have shown that abnormalities, in the calcitonin gene-related peptide (CgRP) activity, could be relevant in the pathogenesis of cryptorchidism. We performed a mutation screening by PCR exon amplification, single-strand conformation polymorphism (SSCP) and sequencing in four candidate genes, CgRPs (alphaCgRP, betaCgRP), their receptor (CgRPR) and the receptor component protein (CgRP-RCP), in 90 selected cases of idiopathic unilateral or bilateral cryptorchidism. Mutation screening of the coding regions and intron-exon boundaries revealed some polymorphic variants but no pathogenic sequence changes. These preliminary data suggest that these genes are not major factors for cryptorchidism in humans.

Adult↗
PubMed2004

Serum levels of malondialdehyde and 4-hydroxy-2,3-nonenal in patients affected by familial chronic nail candidiasis.

Familial chronic nail candidiasis (FCNC.MIM 607644) is a rare disorder characterized by early onset infections caused by different species of Candida and restricted to the nails; this disorder is genetically associated with low serum concentration of intercellular adhesion molecule 1 (ICAM-1). Herein we report the evidence of high circulating levels of malondialdehyde (MDA) and 4-hydroxy-2,3-nonenal (HNE) in seven patients of a five-generation Italian family affected by FCNC.MIM 607644. The present data evidence, in these patients, an increase in circulating MDA and HNE levels. Only some merely speculative hypotheses may be suggested to explain the mechanisms subserving the oxidative stress condition observed in these genetically ICAM-1 deficient patients; however, one has to point out that a chronic oxidative stress condition could contribute to the development of concurrent pathological alterations in which an overproduction of free radicals may play a central role.

Adolescent↗
PubMed2004

Fetal cells in maternal blood: a six-fold increase in women who have undergone amniocentesis and carry a fetus with Down syndrome: a multicenter study.

Fetal nucleated red blood cells (FNRBCs) circulate in the maternal blood throughout pregnancy. Even if the frequency of fetal cells in the maternal circulation remains to be ascertained, complications of pregnancy such as fetal cells aneuploidies, preeclampsia, abnormal Doppler of the uterine artery without symptoms of preeclampsia, fetal growth restriction and polyhydramnios are associated with an increased feto-maternal trafficking. Based on these observations, previous studies have suggested that determination of the fetal nucleated red blood cell count (FNRBCC) might be a useful non-invasive screening test, either alone or in combination with existing maternal tests, for the non-invasive assessment of aneuploidies, in particular Down syndrome (DS). In this paper we have evaluated the distribution of FNRBCC in a set of 18 normal pregnancies and 18 pregnancies with a trisomy 21-affected fetus, matching for gestational age, maternal age, and, when possible, fetal gender, in order to quantify the difference in the number of fetal cells between the two populations. Maternal blood was collected from each pregnant woman two to three weeks after amniocentesis after knowing the cytogenetic results. Correlation of FNRBCC with the gestational week and clinical status (affected vs. non affected) by multiple regression analysis provided significant results (p < 0.001). Adjusted values of FNRBCC were 48 +/- 10.2 in controls and 301 +/- 17.01 in DS cases, corresponding to a 6.27 fold increase. These retrospective results prompt a prospective evaluation of the use of FNRBCC for screening purposes.

Adult↗
PubMed2004

High frequency of subtelomeric rearrangements in a cohort of 92 patients with severe mental retardation and dysmorphism.

About 5-10% of patients with dysmorphisms, severe mental retardation, and normal standard karyotype are affected by subtelomeric chromosome rearrangements. Sequence homology between different chromosomes and variability between homologs make these regions more susceptible to breakage and reunion. We analyzed the telomeric regions of 92 of these patients, selected with strict clinical criteria. Fifteen individuals (16.3%) had subtelomeric rearrangements. Nine had a unique anomaly, which in one case had been inherited from a balanced parent. Six subjects had double segmental imbalances, including three de novo imbalances. This study provides further evidence for the plasticity of subtelomeric regions, which often results in cryptic rearrangements, and recommends stringent criteria for selecting patient candidates to telomere analysis.

Child↗