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Elisa Calzolari

Publications and source records attributed to Elisa Calzolari.

16 recordsLinked to original sources
PubMed2006

Familial occurrence of multiple pterygium syndrome: expression in a heterozygote of the recessive form or variability of the dominant form?

We report on a case with apparently familial multiple pterygium syndrome (MPS). The proposita was a 3-year-old girl with classical symptoms of MPS. A careful clinical examination of the father disclosed the presence of few minor signs of the syndrome, including difficulty in opening the mouth widely, scoliosis, pectus excavatum, hands with slight cutaneous syndactyly, and bilateral single palmar creases. The radiograph of the hands disclosed malformed carpal bones and an altered metacarpal-phalangeal pattern. The father shows limited symptoms, which has been reported before in the autosomal dominant form of MPS. However, it is also possible that he is showing a heterozygous state of the autosomal recessive form of MPS. In conclusion, we emphasize the importance of examining accurately the parents of a child who has classical MPS phenotype, even those with normal stature and an absence of facial anomalies.

Abnormalities, Multiple↗
PubMed2006

A missense mutation in the coiled-coil domain of the KIF5A gene and late-onset hereditary spastic paraplegia.

BACKGROUND: To our knowledge, up to now, only 2 mutations in the KIF5A gene, a member of the kinesin superfamily, have been identified as the molecular cause of early-onset autosomal dominant hereditary spastic paraparesis (ADHSP). OBJECTIVE: To assess the genetic defect in a family with late-onset ADHSP. PATIENTS AND METHODS: Only the proband agreed to undergo complete neurological testing and mutational analysis. The proband was screened for mutations in the spastin, atlastin, NIPA1, and KIF5A genes, either by denaturing high-performance liquid chromatography or sequence analysis. RESULTS: The history of the family was consistent with ADHSP characterized by late onset of the disease. Mutational analysis results were negative for the spastin, atlastin, and NIPA1 genes but identified a missense mutation (c.1082C>T) in the coiled-coil coding region of the KIF5A gene. CONCLUSIONS: This finding enlarges the phenotypic spectrum of ADHSP linked to KIF5A and enhances the role of that gene in the epidemiology of this disease. We propose that the KIF5A gene should be routinely analyzed in patients with hereditary spastic paraplegia negative for spastin and atlastin mutations.

Age of Onset↗
PubMed2006

Trisomy 15 mosaicism owing to familial reciprocal translocation t(1;15): implication for prenatal diagnosis.

We describe a 4-year-old female child with severe global mental retardation, myoclonic epilepsy, proximal hypotonia and dysmorphisms, whose prenatal diagnosis following amniocentesis revealed a constitutional female karyotype carrying a t(1;15)(q10;p11) familial reciprocal translocation. Post-natal high-resolution karyotype, Fluorescence in situ hybridization (FISH) screening for subtelomeric rearrangements, VNTR search for UPD15 in the blood and fibroblast, and WCP1 and 15 in the mother, failed to provide an explanation for the complex clinical phenotype of the proband. Since the pachytene configuration of the translocated chromosomes defines a high probability of 3:1 segregation, an extensive workup was undertaken to look for a possibly cryptic mosaicism. Four percent of the cells with trisomy 15 was found in the peripheral blood lymphocytes examined by classical cytogenetic technique and interphase FISH analysis. The clinical features associated with cryptic trisomy 15 mosaicism and the problems concerning prenatal diagnosis and genetic counselling for carriers of translocations at high risk of 3:1 segregation are discussed.

Adult↗
PubMed2006

Transthyretin RNA profiling in livers from transplanted patients affected by familial amyloidotic polyneuropathy, and identification of a dual transcription start point.

Mutations in the transthyretin (TTR) gene cause familial amyloidotic polyneuropathy (FAP), an autosomal dominant peripheral neuropathy, often associated with cardiomyopathy. Liver transplant currently represents a powerful therapeutic approach for FAP patients, although its efficacy is heavily dependent both on the disease severity and on the cardiac functionality. We have investigated the TTR gene expression searching for tissue-specific additional messengers in human adult and foetal tissues as well as in eight livers from FAP transplanted patients carrying different TTR mutations (Met30, Pro36, Ala47, Arg50, and Gln89). We identified a novel transcript, recognising a different transcription start site. The additional 5'-UTR sequence of this novel transcript contains regulatory boxes possibly highlighting an additional transcription start point. RNA analysis revealed that this region is represented in all foetal/adult tissues analysed. We discussed the implications of this finding which might provide perspectives for better understanding the TTR gene expression.

Amyloid Neuropathies, Familial↗
PubMed2005

Cystathionine beta-synthase c.844ins68 gene variant and non-syndromic cleft lip and palate.

Non-syndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with substantial clinical and social impact and whose causes include both genetic and environmental factors. Folate and homocysteine (Hcy) metabolism have been indicated to play a role in the etiology of CL/P, and polymorphisms in folate and Hcy genes may act as susceptibility factors. We investigated a common polymorphism in the cystathionine beta-synthase (CBS) gene (c.844ins68) in 134 Italian CL/P cases and their parents using the transmission disequilibrium test (TDT). Although no overall linkage disequilibrium was observed, considering the parent-of-origin transmission of the CBS 68 bp insertion a significant (P = 0.002) transmission distortion was detected. When children receive the c.844ins68 allele from the mother compared to the father, they show a 18.7-fold increase in risk for CL/P. This evidence suggests CBS as a candidate gene for CL/P and supports a role of maternal-embryo interactions in the etiology of CL/P.

Alleles↗
PubMed2005

Genomic and transcription studies as diagnostic tools for a prenatal detection of X-linked dilated cardiomyopathy due to a dystrophin gene mutation.

X-linked dilated cardiomyopathy (XLDC) represents a form of dystrophinopathy with exclusive heart involvement. Here a prenatal diagnosis of this condition performed in a family with XLDC is described. In this family, the causative mutation was a pure intronic deletion, which induces the splicing of a novel, aberrant, and out-of-frame exon into the dystrophin transcript. The genetic test was performed by defining both the DNA (villous) and the RNA (amniocyte) configuration. The prenatal diagnosis determined that the fetus was female, and a carrier of the genomic deletion. RNA analysis on cultured amniocytes revealed the presence of an easily detectable dystrophin transcript, as well as the co-existence of both the wild-type and the abnormal splicing profile. Our analysis represents the first report of a prenatal diagnosis in XLDC and also indicates the feasibility of dystrophin mutation detection on RNA from amniocytes. This finding suggests that the dystrophin splicing pattern in amniocytes and skeletal muscle is similar, and that, therefore, this approach could be used in other prenatal dystrophin mutation detection, where abnormal RNA splicing is thought to play a role, or for specific cases in which no mutations have been identified in the coding regions.

Cardiomyopathy, Dilated↗
PubMed2005

Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs.

Genetic testing of the cystic fibrosis transmembrane conductance (CFTR) gene is currently performed in couples undergoing assisted reproduction techniques (ART), because of the high prevalence of healthy carriers in the population and the pathogenic relationship with congenital bilateral absence of vas deferens (CBAVD). However, discordant data have been reported concerning the usefulness of this genetic test in couples with no family history of cystic fibrosis (CF). In this study, we report the results of CFTR molecular screening in 1195 couples entering ART. Genetic testing was initially carried out in a single partner of each couple. CFTR mutations were detected in 55 subjects (4.6%), a percentage that overlaps with the one reported in the general population. However, significantly higher frequencies of were found in CBAVD individuals (37.5%) and in males with nonobstructive azoospermia (6.6%). The 5T allele was found in 78 patients (6.5%). This figure was again significantly different in males with nonobstructive-azoospermia (9.9%) and in those with CBAVD (100%). All together, 139 subjects (11.6%) had either a CFTR mutation or the 5T allele. Subsequent molecular analysis of their partners disclosed a CFTR mutation or 5T allele in nine cases (6.5%). However, none of these couples had CFTR alterations in both members, a CFTR mutation being invariably present in one partner and the 5T allele in the other. In order to improve genetic counselling of these couples, the TG-M470V-5T association was analyzed, and a statistically significant relationship between 12TG-V470 and CBAVD was detected.

Alleles↗
PubMed2004

Toward the effective surveillance of hypospadias.

Concern about apparent increases in the prevalence of hypospadias--a congenital male reproductive-tract abnormality--in the 1960s to 1980s and the possible connection to increasing exposures to endocrine-disrupting chemicals have underlined the importance of effective surveillance of hypospadias prevalence in the population. We report here the prevalence of hypospadias from 1980 to 1999 in 20 regions of Europe with EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers, 14 of which implemented a guideline to exclude glanular hypospadias. We also report data from the England and Wales National Congenital Anomaly System (NCAS). Our results do not suggest a continuation of rising trends of hypospadias prevalence in Europe. However, a survey of the registers and a special validation study conducted for the years 1994-1996 in nine EUROCAT registers as well as NCAS identified a clear need for a change in the guidelines for registration of hypospadias. We recommend that all hypospadias be included in surveillance, but that information from surgeons be obtained to verify location of the meatus, and whether surgery was performed, in order to interpret trends. Investing resources in repeated special surveys may be more cost-effective than continuous population surveillance. We conclude that it is doubtful whether we have had the systems in place worldwide for the effective surveillance of hypospadias in relation to exposure to potential endocrine-disrupting chemicals.

Confounding Factors, Epidemiologic↗
PubMed2004

Quality assessment in cytogenetic and molecular genetic testing: the experience of the Italian Project on Standardisation and Quality Assurance.

The first Italian national trial of external quality assessment in genetic testing was organised within the framework of the "Italian National Project for Standardisation and Quality Assurance of Genetic Tests". Sixty-eight Public Health Service laboratories volunteered for the trial, which involved molecular genetic tests (cystic fibrosis, beta-thalassaemia, familial adenomatous polyposis coli and fragile-X syndrome) and cytogenetic tests (prenatal and postnatal, the latter included cancer cytogenetics). The response rate was high (88.2%). The level of analytical accuracy was good, i.e., the percentage of laboratories that correctly genotyped all samples was 89.3% for cystic fibrosis, 90.9% for beta-thalassaemia, 100% for familial adenomatous polyposis coli (despite two laboratories did not complete the analysis because the amount of DNA was considered insufficient), and 90.5% for fragile-X syndrome. Written reports differed widely and were judged "inadequate" in over 50% of cases. Most laboratories from the present study already have experience in previous European external quality assessments for at least one genetic test; this can explain the higher analytical accuracy in the Italian external quality assessment with respect to quality control programmes in other countries. Collaborative networks are strongly suggested to improve the quality of the reports.

Cystic Fibrosis↗
PubMed2004

Epidemiology of cleft palate in Europe: implications for genetic research.

OBJECTIVE: To describe the epidemiology of cleft palate (CP) in Europe. DESIGN AND SETTING: A descriptive epidemiological study on 3852 cases of CP, identified (1980 through 1996) from more than 6 million births from the EUROCAT network of 30 registers in 16 European countries. RESULTS: Significant differences in prevalence in Europe between registries and within countries were observed. A total of 2112 (54.8%) CP cases occurred as isolated, 694 (18.0%) were associated with other defects such as multiple congenital anomalies, and 1046 (27.2%) were in recognized conditions. The study confirmed the tendency toward female prevalence (sex ratio [SR] = 0.83), particularly among isolated cases (SR = 0.78) even if SR inversion is reported in some registries. A specific association with neural tube defects (NTDs) in some registers is reported. CONCLUSION: The differences identified in Europe (prevalence, sex, associated anomalies) can be only partially explained by methodological reasons because a common methodology was shared among all registries for case ascertainment and collection, and CP is an easy detectable condition with few induced abortions. The complex model of inheritance and the frequently conflicting results in different populations on the role of genes that constitute risk factors suggest the presence of real biological differences. The association of CP/NTD in an area with a high prevalence of NTDs can identify a group of conditions that can be considered etiologically homogeneous. The epidemiological evaluation can guide genetic research to specify the role of etiological factors in each different population

Abnormalities, Multiple↗
PubMed2003

Genomic definition of a pure intronic dystrophin deletion responsible for an XLDC splicing mutation: in vitro mimicking and antisense modulation of the splicing abnormality.

We characterised a dystrophin gene rearrangement in a previously described family with X-linked dilated cardiomyopathy and we demonstrated that it represents an 11 kb deletion occurring within intron 11. This unique deletion joined two physiologically distant intronic regions and brought adjacent two cryptic splice sites, generating a 159 bp sequence recognised as a novel alternative exon and spliced into the dystrophin transcript. Comparative analysis of the intronic region involved in the breakpoint revealed the presence of a LINE1 element (L1P_MA2), containing a 5' unconventional region (L1M1_5). This region provides the 5' cryptic splice site utilised by the novel exon, includes part of the region spliced into the dystrophin transcript and contains two short GA rich regions compatible with splicing motifs. We performed an in vitro splicing assay by using a minigene containing the patient minimal genomic rearrangement and we reproduced the inclusion of the novel alternative exon seen in the patient tissues. Antisense splicing modulation targeting the 3' cryptic splice site succeeded in restoring the canonical splicing. This represents a novel intronic mutational mechanism affecting the dystrophin gene and generating a splicing pathology. The definition of this mechanism might open perspectives in unravelling splicing regulatory motifs and their involvement in human genetic diseases.

Alternative Splicing↗
PubMed2003

Temporal variability in birth prevalence of congenital heart defects as recorded by a general birth defects registry.

OBJECTIVE: Our aim was to examine the temporal variability in congenital heart defect (CHD) birth prevalence from 1980 to 2000 in Emilia-Romagna, Italy. METHODS: The study population consisted of all infants, surveyed by the Emilia-Romagna birth defects registry (Indagine Malformazioni conpenite in Emilia-Romagna [IMER]), who were affected by CHDs. A simplified classification into "simple" and "complex " CHD was adopted. A comparison with another epidemiologic study using different methodology in the same area was performed. RESULTS: From 1980 to 2000, IMER ascertained 2442 live births with CHD of 480,793 infants born, with an average CHD birth prevalence of 5.1% (Range, 3.1% to 7.5%). A significant increase in prevalence of simple CHD during the second decade of the study was demonstrated because of an increased recognition of "minor" cardiac lesions among the simple CHD. The birth prevalence of complex CHD remained stable. CONCLUSIONS: The apparent increase in live births with CHD results mainly from the current widespread availability of color Doppler echocardiography, which allows the early detection of the "minor" cardiac defects. Other differences are the result of the sources of ascertainment, diagnostic criteria, system of classification, and especially the age limit for enrolling infants with suspected CHD.

Female↗
PubMed2003

Progress in understanding GJB2-linked deafness.

Mutations in the GJB2 gene (encoding for Connexin 26 protein) represent a leading cause of genetic hearing impairment. Extensive epidemiological and molecular studies have been reported, describing GJB2 mutations type, frequency and distribution. Moreover, several aspects of GJB2 mutations pathogenic effects have been elucidated taking advantage of in vitro and in vivo experimental approaches. Progress through reported studies is reviewed, highlighting recent major achievements in this field. Attention is focused on different unresolved questions regarding GJB2 deafness pathogenesis and genotype-phenotype relationships. Clarification of these important clues will significantly increase our understanding of the molecular basis of hearing loss and will improve the effectiveness of diagnosis and counselling of this frequent disease.

Connexin 26↗
PubMedDate not supplied

FISH screening for subtelomeric rearrangements in 219 patients with idiopathic mental retardation and normal karyotype.

Subtelomeric rearrangements are a common cause of idiopathic mental retardation (MR) accounting for 6.3-10.2% of moderate to severe cases and less than 1% of mildly retarded patients. We report on a cohort of 219 patients with idiopathic MR and normal 400-550 band karyotype screened for subtelomeric rearrangements by multiprobe Fluorescence in situ hybridization (FISH) in three Italian Genetics Centers. Twelve positive cases (5.5%) were found. Six were de novo deletions (1p, 7p, 9p, 9q, 20p, 22q) and four unbalanced translocations [a der(6)t(6q; 18p) and a der(18)t(8p; 18q) both de novo, a der(12)t(12p; 17q)mat and a der(2)t(2q; 17q) of unknown origin]. The remaining two cases were apparently balanced reciprocal translocations [a t(4p; 18q) and a t(1p; 16p)] of undetermined origin whose role in the pathogenesis of the clinical phenotype is doubtful. Dysmorphic features were present in all unbalanced patients, whilst a family history of MR was present in only four of them. The proposition that subtelomeric rearrangements are a significant cause of idiopathic MR is supported by our survey. Collection of the clinical data of positive patients will help to delineate the phenotype associated with the various subtelomeric abnormalities, to tailor healthcare services to the needs of these patients and their families and to determine the appropriate use of the test.

Adolescent↗
PubMedDate not supplied

Preventing neural tube defects in Europe: a missed opportunity.

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large-scale prevention of NTDs.

Adult↗