PubMed Health⌕ Search

Biomedical subjects

R Tenconi

Publications and source records attributed to R Tenconi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Down syndrome and parity.

OBJECTIVE: To investigate the effect of parity on Down syndrome (DS). METHODS: The study was conducted on data from Northeast Italy (NEI) (1981-1996) and Sicily (ISMAC) (1991-1996) Congenital Malformation Registries. In these areas, all DS births are recorded and confirmed by chromosomal analysis; the NEI Registry also registers pregnancy terminations (TOPs) after prenatal diagnosis of DS. In order to estimate the effect of parity independently of the mother's age and to reduce the truncation effect, different age classes and three classes of parity (1, 2-4, >4) were defined. RESULTS: The study sample consisted of 1,088 consecutive newborns and 169 consecutive fetuses affected by DS. In both NEI and ISMAC samples, we found a significantly increased risk of having a DS child for multiparas > or =35 years of age. In the NEI sample, the inclusion of TOP data did not seem to modify this finding. In the ISMAC sample, a significantly reduced risk for primiparas was found at all ages. CONCLUSIONS: Our data confirm a higher risk of having a DS child in women with parity >4. As this effect is evident only in women > or =35 years age, its practical impact is null because these women are usually offered prenatal diagnosis in any case. However, the mechanisms involved, if this association is true, are very intriguing and the observation should stimulate scientific studies allowing a better knowledge of the nondisjunction mechanism.

Journal Article↗
PubMed1998

STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer.

A potential tumor suppressor gene, STK11 , encoding a serine threonine kinase, has recently been identified on chromosome 19p13. Germ-line mutations of this gene have been found in patients with Peutz-Jeghers syndrome (PJS). To further investigate the relevance of STK11 mutations in PJS, we analyzed its coding sequence in nine patients and identified two deletions and three missense mutations. Because intestinal carcinomas have been observed to develop in association with PJS, we analyzed tumors from 71 patients for allelic deletions (loss of heterozygosity) and STK11 gene mutations, to elucidate the etiological role of STK11 gene in sporadic colorectal cancer. Loss of heterozygosity, evaluated using the microsatellite D19S886, was observed in 10 of 52 informative cases. No somatic mutations were detected except for a missense alteration in one tumor. Our data indicate the heterogeneity of PJS and the infrequent involvement of the STK11 gene in colorectal cancer.

AMP-Activated Protein Kinase Kinases↗
PubMed1998

Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study.

BACKGROUND: Waste-disposal sites are a potential hazard to health. This study is a multicentre case-control study of the risk of congenital anomalies associated with residence near hazardous-waste landfill sites in Europe. METHODS: We used data from seven regional registers of congenital anomalies in five countries. We studied 1089 livebirths, stillbirths, and terminations of pregnancy with non-chromosomal congenital anomalies and 2366 control births without malformation, whose mothers resided within 7 km of a landfill site; 21 sites were included. A zone within 3 km radius of each site was defined as the "proximate zone" of most likely exposure to teratogens. FINDINGS: Residence within 3 km of a landfill site was associated with a significantly raised risk of congenital anomaly (295 cases/511 controls living 0-3 km from sites, 794/1855 living 3-7 km from sites; combined odds ratio 1.33 [95% CI 1.11-1.59], adjusted for maternal age and socioeconomic status). There was a fairly consistent decrease in risk with distance away from the sites. A significantly raised odds ratio for residence within 3 km of a landfill site was found for neural-tube defects (odds ratio 1.86 [1.24-2.79]), malformations of the cardiac septa (1.49 [1.09-2.04]), and anomalies of great arteries and veins (1.81 [1.02-3.20]). Odds ratios of borderline significance were found for tracheo-oesophageal anomalies (2.25 [0.96-5.26]), hypospadias (1.96 [0.98-3.92]), and gastroschisis (3.19 [0.95-10.77]). There was little evidence of differences in risk between landfill sites but power to detect such differences was low. INTERPRETATION: This study shows a raised risk of congenital anomaly in babies whose mothers live close to landfill sites that handle hazardous chemical wastes, although there is a need for further investigation of whether the association of raised risk of congenital anomaly and residence near landfill sites is a causal one. Apparent differences between malformation subgroups should be interpreted cautiously.

Case-Control Studies↗
PubMed1998

Schwartz-Jampel syndrome type 2 and Stüve-Wiedemann syndrome: a case for "lumping".

Recent studies demonstrated the existence of a genetically distinct, usually lethal form of the Schwartz-Jampel syndrome (SJS) of myotonia and skeletal dysplasia, which we called SJS type 2. This disorder is reminiscent of another rare condition, the Stüve-Wiedemann syndrome (SWS), which comprises campomelia at birth with skeletal dysplasia, contractures, and early death. To test for possible nosologic identity between these disorders, we reviewed the literature and obtained a follow-up of the only two surviving patients, one with SJS type 2 at age 10 years and another with SWS at age 7 years. Patients reported as having either neonatal SJS or SWS presented a combination of a severe, prenatal-onset neuromuscular disorder (with congenital joint contractures, respiratory and feeding difficulties, tendency to hyperthermia, and frequent death in infancy) with a distinct campomelic-metaphyseal skeletal dysplasia. The similarity of the clinical and radiographic findings is so extensive that these disorders appear to be a single entity. The follow-up observation of an identical and unique pattern of progressive bone dysplasia in the two patients (one with SJS type 2, one with SWS) surviving beyond infancy adds to the evidence in favor of identity. The hypothesis that SWS and SJS type 2 are the same disorder should be testable by molecular methods.

Abnormalities, Multiple↗
PubMed1998

The familial adenomatous polyposis region exhibits many different haplotypes.

In the present study, we used five different polymorphic markers to construct the haplotype at the adenomatous polyposis coli (APC) locus in families with familial adenomatous polyposis (FAP) and in the normal Italian population. Non-ambiguous haplotypes were reconstructed from 246 normal chromosomes and 65 FAP chromosomes. In the control population, the four polymorphisms intragenic to APC gave rise to 16 haplotypes, the most common of which (II and XV) accounted for over 50% of all chromosomes. In FAP patients, 13 haplotypes were found but their distribution was not statistically different from normal subjects. Eighty complete chromosomal haplotypes (many fewer than the theoretical maximum of 208) for the five polymorphic sites assayed were observed in the control population, 35 being found in the FAP patients. We compared the distribution of these haplotypes within the two groups; no statistically significant differences between normal and FAP chromosomes were found. The elevated heterogeneity of FAP chromosomes was clearly confirmed by the observation that 19 patients who carried one or other of the two most common APC mutations (nt 3183 and nt 3927) showed 18 different haplotypes. On the basis of these results, we were not able to identify a founder FAP chromosome. Various mechanisms are presented to explain this observation.

Adenomatous Polyposis Coli↗
PubMed1998

Cardiovascular anomaly in Rieger Syndrome: heterogeneity or contiguity?

PURPOSE: Rieger Syndrome (RS) is an autosomal dominant disease, in which Axenfeld's and Rieger's anomalies are associated with typical facial dysmorphism and other extra-ocular findings. Cardiovascular defects are considered an occasional finding in this syndrome. METHODS: We describe a RS case in which the typical ocular and dysmorphic features were associated with bicuspid aortic valve. A review of the literature is provided. RESULTS: A total of 15 other cases of Axenfeld's or Rieger's anomaly associated with cardiovascular defects have been reported. In the cases in which the diagnosis of RS could be clinically performed, the cardiac defect mostly involved the outflow tract structures. CONCLUSION: The hypothesis that this association could be non-coincidental is discussed. The proved genetic heterogeneity of RS, based on clinical and molecular evidence, may suggest that RS is a contiguous gene syndrome or RS with cardiac defect is a separate entity. Finally we suggest a careful cardiological evaluation in RS patients, to assess the real frequency of cardiac defects in this syndrome.

Abnormalities, Multiple↗
PubMed1998

Inheritance of astigmatism: evidence for a major autosomal dominant locus.

Although astigmatism is a frequent refractive error, its mode of inheritance remains uncertain. Complex segregation analysis was performed, by the POINTER and COMDS programs, with data from a geographically well-defined sample of 125 nuclear families of individuals affected by astigmatism. POINTER could not distinguish between alternative genetic models, and only the hypothesis of no familial transmission could be rejected. After inclusion of the severity parameter, COMDS results defined a genetic model for corneal astigmatism and provided evidence for single-major-locus inheritance. These results suggest that genetic linkage studies could be implemented and that they should be limited to multiplex families with severely affected individuals.

Adult↗
PubMed1997

Blastogenesis dominant 1: a sequence with midline anomalies and heterotaxy.

Lateralization defect is a heterogeneous condition with different modes of transmission (autosomal recessive, dominant or X-linked). Here, we report on 3 additional families that contribute to the description of phenotypic anomalies of the autosomal dominant type. Phenotypic anomalies include: lateralization defects, cardiac malformations, diaphragmatic hernia, urologic and neurologic anomalies. We suggest calling this sequence BGD1 for blastogenesis dominant 1 because the deleterious effect probably occurs during blastogenesis and involves not only lateralization but other defects as well.

Abnormalities, Multiple↗
PubMed1997

Family with branchial arch anomalies, hearing loss, ear and commissural lip pits, and rib anomalies. A new autosomal recessive condition: branchio-oto-costal syndrome?

We report on a family in which 3 sibs were affected with conductive deafness, bilateral preauricular and commissural lip pits, monolateral branchial fistula, and rib anomalies. On the basis of parental consanguinity, lack of clinical variability and affected subjects of both sexes, this condition seems to be inherited as an autosomal recessive trait. We suggest that these findings comprise a new autosomal recessive entity of branchial, auricular and costal anomalies, for which we suggest the acronym BOC (branchio-oto-costal) syndrome.

Abnormalities, Multiple↗
PubMed1997

Inheritance of cleft palate in Italy. Evidence for a major autosomal recessive locus.

Although several studies have demonstrated familial aggregation of nonsyndromic cleft palate (CP), the mode of inheritance still remains uncertain. We report the results of complex segregation analysis performed in families of 357 consecutive newborns affected with nonsyndromic CP (i.e., CP not a component feature of malformation syndrome, sequence or association), and registered in the North East Italy and Emilia Romagna congenital malformation registries in the period 1981-1993. This sample, based on a large number of consecutive births, in a well-defined geographical area, with quality control to detect associated anomalies and malformation syndromes, is independent of the number of affected subjects in the family and of CP severity, fitness, and survival. We have analyzed, using the mixed model, the whole sample of nonsyndromic CP, including isolated (i.e., without other anomalies) CP (CPI) and CP associated with at least one other anomaly (CPA), for which a diagnosis of malformation syndrome was not possible. When nonsyndromic CP (including CPA) are considered in the analysis, there is no heterogeneity between CPA and CPI nor between CP including hard palate (CPH) and CP of the soft palate only (CPS). POINTER and COMDS programs cannot discriminate between alternative genetic models; only the hypothesis of non-genetic transmission is rejected. The COMDS analysis two-locus model, which indicates that a modifier locus (or loci) operates in addition to a single major locus (SML), does not show evidence of better fit than SML, polygenic, and multifactorial models. When the severity parameter (defined as CPH and CPS) is added, CPI and CPA show heterogeneity. Eventually, when the analysis is limited to CPI and includes information on severity, a recessive SML, with low penetrance and determining CPH, provides a significant best fit. To have defined a genetic model for CPI and provided evidence for SML inheritance suggests that genetic linkage studies could be implemented. This conclusion is in agreement with previous studies which showed a significant association between alleles of transforming growth factor alpha and CP only in humans, and that single recessive genes may play a crucial role during palatogenesis in mice as well as in Brittany spaniels. Application of the candidate genes to human CPH families could reveal whether these genes are involved.

Alleles↗
PubMed1997

Clinical and genetic heterogeneity in Meckel syndrome.

Meckel syndrome (MKS) is a lethal malformation syndrome characterised by posterior meningoencephalocele, polycystic kidneys, fibrotic changes of the liver, and polydactyly. We have previously shown a linkage to chromosome 17q in 17 Finnish Meckel families. In this study we have analysed one Italian, one Austrian (of Turkish origin) and three British MKS families (Caucasian, Pakistani, and Bangladeshi families) for linkage to the MKS locus on chromosome 17q22-q24. We did not observe co-segregation of the disease and marker haplotypes in the Austrian family or in the three British families, of which two represented classical MKS and one a slightly atypical MKS phenotype with longer survival of the patient. In the Italian family the affected and non-affected children did not share the same maternal chromosome and thus this family could represent the same allelic disease as the Finnish MKS families. These results suggest locus heterogeneity in Meckel syndrome--a feature previously suspected based on the highly variable clinical phenotype.

Abnormalities, Multiple↗
PubMed1996

Stüve-Wiedemann dysplasia in a 3 1/2-year-old boy.

Stüve-Wiedemann osteochondrodysplasia is a rare disorder with distinct clinical and diagnostic radiographic findings. The condition is classified as a bent-bone dysplasia with early, lethal outcome. We report on a boy with Stüve-Wiedemann syndrome who is well and alive at the age of 3 1/2 years.

Bone and Bones↗
PubMed1996

Familial congenital bicuspid aortic valve: a disorder of uncertain inheritance.

Congenital bicuspid aortic valve (BAV) is one of the most frequent heart defects detected by echocardiographic investigation and necropsy (0.9-1% of the general population), but only 16 families with familial congenital BAV have been described up to now. We report on a family in which 4 members of two generations (2 brothers, 1 sister, and her son) are affected with BAV. The BAV mode of inheritance is discussed.

Adult↗
PubMed1996

Anesthesiologic problems in Williams syndrome: the CACNL2A locus is not involved.

We present the case of a patient affected with Williams syndrome (WS), who developed a suspected malignant hyperthermia (MH) reaction to general anesthesia. The proximity to the WS region of the gene encoding the L-type voltage-gated calcium channel alpha 2/delta-subunit (CACNL2A) on 7q11.23-q21.1, previously shown to be closely linked to some forms of MH susceptibility, prompted us to investigate whether this gene is deleted in WS. Linkage studies and fluorescence in situ hybridization analysis demonstrated that the CACNL2A locus is localized outside the WS deleted region.

Adolescent↗
PubMed1996

Sex differences in mutational rate and mutational mechanism in the NF1 gene in neurofibromatosis type 1 patients.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a prevalence of around 1 in 3500, affecting all ethnic groups. The clinical manifestations of the disease are variable, even among members of the same family, and affect a variety of tissues and cell types, including skin, iris, central and peripheral nervous systems and skeletal system. It has been reported that the majority of sporadic mutations in NF1 arise in paternally inherited alleles. We present here a collaborative study of the parental origin and type of mutation in individuals with de novo NF1, who account for up to a half of all cases of clinically diagnosed NF1. We have studied intragenic and extragenic markers in 470 NF1 families. In 32 of these families it was possible to assess the parental origin of a de novo NF1 mutation either by linkage analysis (in families with three generations) or by the detection of an intragenic deletion in a sporadic NF1 case. Eleven of these 32 families have three generations (the second and third generation being affected), with the mutation (not a large deletion) being of paternal origin in 82% of them (P < 0.05). In the other 21 families an intragenic deletion was detected, in 76% being in the maternal chromosome and in 24% in the paternal one (P < 0.05). Our results suggest that in NF1 the majority of deletions occur in oogenesis, while other types of mutations should account for the paternally derived NF1 mutations.

Chromosome Mapping↗
PubMed1996

Headache in patients with neurofibromatosis type 1.

A study of headache in a homogeneously ascertained population of 181 subjects suffering from neurofibromatosis type 1 is described. All subjects underwent a diagnostic protocol including imaging studies (for subjects over 5 years old up until 1992). Headache data were collected by means of a questionnaire. Headache was present in 55 of 181 subjects (25 males). Overall headache frequency was 30%, which is not significantly different from the frequency of headache reported in the general population. Headache was primary in 52 cases (5 migraine and 47 tension-type) and secondary to obstructive hydrocephalus with brain tumor-induced intracranial hypertension in 3 with a tension-type pattern. It was concluded that headache is not a specific feature of neurofibromatosis type 1, it is not significantly related to central nervous system abnormalities, and in itself, it is not an indication for neuroradiological examination.

Adolescent↗
PubMed1996

Clinical application of genetic polymorphism in neurofibromatosis type 1.

The authors report the study of DNA polymorphic sequences, 5 intragenic and 5 flanking the NF1 gene, in 87 Italian NF1 families for a total of 142 affected individuals and 204 non-affected relatives. All PCR-based analyses are easy and simple to perform, and require small amounts of DNA. The non radioactive method used is sensitive, rapid, and has low background. All subjects were informative for at least 2 markers. The use of linkage study to familial cases allowed us to exclude the diagnosis prenatally in two fetuses, and to confirm or exclude diagnosis in those relatives with clinical signs, but not fulfilling the international diagnostic criteria. Furthermore indirect analysis permitted the detection of large gene deletions by loss of heterozygosity of one or more DNA markers in three out of 47 sporadic cases.

Female↗