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Biomedical subjects

B Dallapiccola

Publications and source records attributed to B Dallapiccola.

At least 73 records · Page 4Linked to original sources
PubMed2001

A single strand conformation polymorphism-based carrier test for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a newborn prevalence of 1 in 10,000, and a carrier frequency of 1 in 40-60 individuals. The SMA locus has been mapped to chromosome 5q11.2-13. The disease is caused by a deletion of the SMN gene, often encompassing other genes and microsatellite markers. The SMN gene is present in two highly homologous copies, SMN1 and SMN2, differing at five nucleotide positions. Only homozygous SMN1 mutations cause the disease. The sequence similarity between the SMN1 and SMN2 genes can make molecular diagnosis and carrier identification difficult. We developed a sensitive and reliable molecular test for SMN1 carrier identification, by setting up a nonradioactive single strand conformation polymorphism (SSCP)-based method, which allows for the quantification of the amount of the SMN1 gene product with respect to a control gene. The assay was validated in 56 obligate (ascertained) carriers and 20 (ascertained) noncarriers. The sensitivity of the test is 96.4%, and its specificity, 98%. In addition, 6 of 7 SMA patients without homozygous deletions presented with a heterozygous deletion, suggesting a concomitant undetected point mutation on the nondeleted SMN1 allele. Therefore, the present test is effective for detecting compound hemizygote patients, for testing carriers in SMA families, and for screening for SMA heterozygotes in the general population.

Alleles↗
PubMed2001

Coeliac disease in Williams syndrome.

BACKGROUND: Coeliac disease (CD) has been reported in several patients affected by chromosomal disorders, including Down syndrome (DS) and Turner syndrome (TS). CD has also been found in sporadic Williams syndrome (WS) patients. In this study, CD was evaluated in a consecutive series of patients with WS, in order to estimate if the prevalence of CD in WS patients is higher than in the general population. METHODS AND RESULTS: A consecutive series of 63 Italian patients with WS was studied by analysing the dosage of antigliadin antibodies (AGA) IgA and antiendomisium antibodies (AEA). In patients with positive AGA and AEA, small bowel biopsy was performed. The prevalence of CD in our WS population was compared with that estimated in a published series of 17 201 Italian students. Seven WS patients were found to be positive for AGA IgA and AEA. Six of them underwent small bowel biopsy, which invariably disclosed villous atrophy consistent with CD. The prevalence of CD in the present series of WS patients was 9.5% (6/63), compared to 0.54% (1/184) in the Italian students (p<0.001). CONCLUSION: The present results suggest that the prevalence of CD in WS is higher than in the general population and is comparable to that reported in DS and TS. AGA and AEA screening is recommended in patients with WS.

Adolescent↗
PubMed2001

Cloning and molecular characterization of three ubiquitin fusion degradation 1 (Ufd1) ortholog genes from Xenopus laevis, Gallus gallus and Drosophila melanogaster.

The yeast ubiquitin fusion degradation 1 (Ufd1) protein is involved in a degradation pathway for ubiquitin fused products. The human ortholog gene (UFD1-like, UFD1L) is deleted in patients affected by the DiGeorge/velocardiofacial syndromes. We report the cloning of UFD1L orthologs from Drosophila melanogaster (dufd1l), Xenopus laevis and Gallus gallus. The 1,125-bp Drosophila cDNA encodes a protein of 316 amino acids, showing 60% identity with the human and murine proteins. The identity to the G. gallus, X. laevis, C. elegans and S. cerevisiae proteins is 95%, 83%, 32%, and 36%, respectively. Northern expression data in Drosophila indicate that dufd1l is expressed through embryonic, larval and pupal development, as well as in the adult fly.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Pulmonary atresia with ventricular septal defect: prevalence of deletion 22q11 in the different anatomic patterns.

BACKGROUND: Pulmonary atresia with ventricular septal defect (PA-VSD) is one of the most common cardiac defects associated with DiGeorge syndrome. The pattern of the pulmonary circulation determines the complexity of this type of heart disease. The aim of this study was to establish the prevalence of DiGeorge syndrome with deletion 22q11 in patients with simple and complex PA-VSD. METHODS: Since 1993 we have studied 128 consecutive patients affected by PA-VSD. In 90 of our patients the PA-VSD was considered "simple" (group I), because it was not associated with any other cardiac defects. In the other 38 children the PA-VSD was considered "complex" (group II) owing to the presence of heterotaxia, tricuspid atresia, a double-inlet left ventricle, transposition of the great arteries and congenitally corrected transposition of the great arteries. RESULTS: In group I, 38 patients (42%) had genetic syndromes or major extracardiac anomalies; deletion 22q11 was detected in 31% of cases. Major aortopulmonary collateral arteries were present in 50% of group I patients and in 57% of those with deletion 22q11. In group II, 10 patients (26%) had genetic syndromes or major extracardiac anomalies but none had deletion 22q11 (p < 0.005); in no case was the presence of major aortopulmonary collateral arteries observed (p < 0.005). CONCLUSIONS: PA-VSD is an anatomically and morphogenetically heterogeneous disease: in the setting of DiGeorge syndrome or velocardiofacial syndrome, PA-VSD is associated with a peculiar cardiac pattern and is due to deletion 22, whereas in case of nonsyndromic PA-VSD or when this disease is associated with different syndromes or with other types of cardiac defects, it is due to other morphogenetic mechanisms.

Child Welfare↗
PubMed2000

Heterotaxy with left atrial isomerism in a patient with deletion 18p.

We report on a female infant with partial deletion of the short arm of chromosome 18 (del 18p) and heterotaxy with left atrial isomerism. Congenital heart defect (CHD) is found in 10% of the literature reports. Interestingly, situs abnormalities have been diagnosed in four patients with del 18p, including ours. This finding could imply that a locus or loci involved in the development of normal body situs lies within this chromosomal region. Del 18p must be consid- ered when evaluating a patient with phenotypic anomalies and CHD in lateralization defects.

Chromosome Deletion↗
PubMed2000

Mapping a dominant form of multinodular goiter to chromosome Xp22.

Multinodular goiter (MNG) is a common disorder characterized by a nodular enlargement of the thyroid gland and occurring with a female&rcolon;male ratio of 5&rcolon;1. This article reports the analysis of an Italian three-generation pedigree MNG, including 10 affected females and 2 affected males. After linkage to candidate regions previously implicated in various forms of goiter was excluded, a novel MNG locus was searched. Because no male-to-male transmission was present in the study pedigree, an X-linked autosomal dominant pattern of inheritance was hypothesized. Therefore, 18 markers spaced at 10-cM intervals on the X chromosome were examined. A significant LOD score was observed in the Xp22 region, where marker DXS1226 generated a maximum LOD score of 4.73 at a recombination fraction of 0. Analysis of six flanking microsatellites confirmed these data, and haplotype inspection delimited a 9.6-cM interval lying between DXS1052 and DXS8039.

Chromosome Mapping↗
PubMed2000

Deletion of a 5-cM region at chromosome 8p23 is associated with a spectrum of congenital heart defects.

BACKGROUND: Cytogenetic evidence suggests that the haploinsufficiency of > or =1 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs. METHODS AND RESULTS: We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at approximately 10 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at approximately 10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion. CONCLUSIONS: Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs.

Adolescent↗
PubMed2000

Familial recurrence of nonsyndromic interrupted aortic arch and truncus arteriosus with atrioventricular canal.

BACKGROUND: Multifactorial inheritance is probably involved in most cases of nonsyndromic conotruncal heart defects (CHDs), but Mendelian transmission is often suspected. RESULTS: We report on a family with recurrence of nonsyndromic CTHD in two double first cousins; i.e., two brothers married two sisters. One of the cousins (case 1) had interrupted aortic arch (IAA) type B, while the other one (case 2) had truncus arteriosus (TA) with atrioventricular canal defect (AVCD). CONCLUSIONS: Our family further supports monogenic inheritance of CTHDs. In addition, the presence of TA associated with AVCD in one of the patients confirms the higher occurrence of CTHD in families with complex TA. The absence of 22q11 microdeletion (del22q11) in our patients, as in several literature reports of familial CTHDs, supports the existence of genes different to those located on chromosome 22q11 which could be implicated in the pathogenesis of CTHDs.

Aorta, Thoracic↗
PubMed2000

Absence of correlation between BMP-4 polymorphism and postmenopausal osteoporosis in Italian women.

Several studies have demonstrated that bone has the power of regeneration and repair. BMPs (bone morphogenetic proteins) are involved in the determination of osteoblast phenotype and bone turnover, therefore genes coding for these proteins, like BMP-4, could be considered potential candidate genes for osteoporosis. We investigated the association of BMP-4 gene polymorphism with osteoporosis in a cohort of 72 osteoporotic, postmenopausal women and 82 unrelated controls. We failed to detect any significant association between this genetic marker and the disease.

Bone Morphogenetic Protein 4↗
PubMed2000

Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis.

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.

Alternative Splicing↗
PubMed2000

Fine mapping of a distinctive autosomal dominant vacuolar neuromyopathy using 11 novel microsatellite markers from chromosome band 19p13.3.

We previously mapped a distinctive autosomal dominant vacuolar neuromyopathy on human chromosome 19p13 in an 8cM region, delimited by D19S209 and D19S177 markers. We now report the fine mapping of the disease locus within an interval of 250 Kb by haplotype analysis performed using a set of 11 novel microsatellite markers isolated from the candidate region.

Chromosome Mapping↗
PubMed2000

T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome.

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Abnormalities, Multiple↗
PubMed2000

Evidence for an association between the SRD5A2 (type II steroid 5 alpha-reductase) locus and prostate cancer in Italian patients.

We have investigated the contributions of three polymorphic markers in the SRD5A2 gene to prostate cancer in a group of Italian patients. We have genotyped cases and controls for a polymorphic (TA)n dinucleotide repeat and two functional substitutions, A49T and V89L, substituting respectively alanine with threonine at codon 49, and valine to leucine at codon 89. We found a substantially increased but not significant risk associated with the 49T mutation and a reduction of risk for the V89L substitution. In conclusion, we report on preliminary evidence for both increased and decreased risk associated with separate markers at this locus.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗