Search PubMed⌕ Search

Biomedical subjects

G A Danieli

Publications and source records attributed to G A Danieli.

At least 19 recordsLinked to original sources
PubMed1995

Dystrophin-positive fibers in Duchenne dystrophy: origin and correlation to clinical course.

In 132 DMD muscle biopsies we investigated the presence of dystrophin-positive fibers and the relationship of dystrophin immunohistochemical pattern to the clinical severity of the disease. Reverted fibers were detected in 37% of patients; their prevalence increased significantly in each biopsy with age of patients. We suggest that reversion occurs in satellite cells, when muscle differentiation is completed. The longitudinal extent of dystrophin-positive domain spans a maximum length of 900 microns. No correlation was found between the presence of reverted fibers and the clinical severity of DMD, whereas a milder form of Duchenne dystrophy was observed in patients showing a faint reaction in all fibers. The occurrence of reverted fibers is independent of the type of gene mutation; however, a higher proportion of cases with reverted fibers was found among patients with gene duplications.

Biopsy↗
PubMed1995

Genetic control of the CD4/CD8 T-cell ratio in humans.

We studied the genetic pattern of inheritance of the ratio between circulating CD4+ and CD8+ T lymphocytes in a population of healthy donors. The distribution of the CD4/CD8 ratio in males and females was significantly different and was significantly affected by age. In 46 randomly selected families, the parental CD4/CD8 ratio significantly influenced the ratio in offspring. Complex segregation analysis of the data rejected the non-genetic hypothesis; among the genetic models tested, a major recessive gene with a polygenic component and random environmental effects was the most parsimonious model. These findings indicate that the ratio of CD4+ and CD8+ T cells is genetically controlled in humans.

Adult↗
PubMed1994

Non-radioactive detection of 17p11.2 duplication in CMT1A: a study of 78 patients.

Charcot-Marie-Tooth disease type 1 (CMT1) is a peripheral neuropathy characterised by progressive distal muscular atrophy and sensory loss with markedly decreased nerve conduction velocity, mostly inherited as an autosomal dominant trait. The most common form, type 1A, is associated with a 1.5Mb DNA duplication in region p11.2-p12 of chromosome 17 in many patients. In this study a non-radioactive test for detection of the CMT1A duplication based on an RM11-GT microsatellite polymorphism is presented. Although different methods have been devised for this purpose, the present method has the advantage of being rapid, informative, economical, easily interpretable, and, therefore, it represents a very useful tool for diagnosis of CMT1A, especially before clear manifestation of clinical symptoms. Seventy-eight patients diagnosed clinically as having CMT and evaluated by electrophysiological methods were tested with an RM11-GT microsatellite and with probe pVAW409R3. The CMT1A duplication was found in 76% of the 56 unrelated patients. RM11-GT was the most informative marker with a heterozygosity of 89%.

Base Sequence↗
PubMed1994

A report on 528 intragenic deletions detected in DMD and BMD patients by an Italian collaborative study.

The results of a collaborative study involving about one third of the total DMD and BMD cases living in the Italian territory are reported. The analysis of the breakpoint frequency by intron revealed significant differences among regional groups of DMD patients (for introns 2, 11 and 50 in Sardinia and for introns 9 and 45 in northeastern Italy), whereas no regional differences were observed among regional groups of BMD patients. These differences involve the same Italian regions which previous studies, performed by different markers, identified as "genetically differentiated". The data support the possibility of a differential distribution among populations of some intronic sequences, facilitating the origin of deletion breakpoints within the dystrophin gene.

Dystrophin↗
PubMed1992

Further evidence of a duplication in 17p11.2 in families with recurrence of HMSN Ia (Charcot-Marie-Tooth neuropathy type Ia).

Five Italian families with recurrence of cases of Charcot-Marie-Tooth disease (type Ia) were analysed using three closely linked DNA probes that detect polymorphisms in the region 17p11.2. The probe pVAW409R3 detected the presence of a duplication in all the affected subjects, but not in the subjects with normal electromyographic (EMG) findings. This observation confirms previous data indicating the association of the duplication with the disease, suggesting that, at least in populations of European origin, the duplication might be the molecular feature diagnostic of the pathological trait.

Charcot-Marie-Tooth Disease↗
PubMed1992

Prevalence of dystrophin-positive fibers in 85 Duchenne muscular dystrophy patients.

The prevalence of dystrophin-positive fibers in Duchenne muscular dystrophy (DMD) muscle was estimated by direct counting on immunostained sections in a series of biopsy specimens from 85 patients, 42 of which were also screened for intragenic deletions by cDNA probes. Dystrophin-positive fibres are normotrophic and occur in muscle sections at a frequency between 0.01 and 6.81%. Frequencies over 1% were found only in patients older than 6 yr. The prevalence of dystrophin-positive fibers is about the same in patients with detectable and with undetectable deletions. The occurrence of positive fibers in small clusters supports the hypothesis of their clonal origin, suggesting that they may result from genetic reversion. No clinical differences were noticed in DMD patients of similar age with respect to the occurrence of dystrophin-positive fibres in their muscle biopsies.

Aging↗
PubMed1992

Screening for mutations in the muscle promoter region and for exonic deletions in a series of 115 DMD and BMD patients.

Mutations in the muscle promoter region and exonic deletions were screened in a series of 115 unrelated DMD and BMD patients from north-east Italy. No gross mutations of the promoter region were found. In three cases in which dystrophin of normal size was expressed at low levels, the analysis of DNA sequences of the promoter region failed to detect abnormalities. The majority of deletions in coding sequences, detected by cDNA probes, occur in the deletion hot spot identified by the probe P20. Intrafamilial variability in the severity of the disease is reported and discussed.

Adolescent↗
PubMed1992

Epidemiology of spinal muscular atrophies in a sample of the Italian population.

In the course of an epidemiological survey in four provinces of Veneto (northeastern Italy) 67 spinal muscular atrophy (SMA) cases (types I, II and III) were recorded. The survey spanned the period 1960-1983 and involved 859,891 consecutive live-born infants in a population of 2,635,800 inhabitants. The overall prevalence at birth for SMA types I, II and III was 7.8/100,000 live births. Type I alone accounted for 4.1/100,000 live births. If the hypothesis that SMA types I, II and III are clinical manifestations of allelic mutations is assumed, the mutation rate would be about 70 x 10(-6) and the frequency of the heterozygotes 1 in 57.

Female↗
PubMed1991

Genetic epidemiology of hereditary motor sensory neuropathies (type I).

Patients affected with hereditary motor sensory neuropathy (HMNS) type I were traced through hospital records. Each case was re-examined, a family history was drawn, and EMG examination was performed in those members of the family who could have inherited the trait. In the prevalence year 1987, in a population of 1,067,130 inhabitants of 2 contiguous provinces of northeast Italy, 100 living cases were recorded in 30 families, giving a minimal prevalence rate estimate of 9.37/100,000. HMSN I is inherited as an autosomal dominant trait, when clinical evaluation includes EMG. No difference may be established clinically between the 2 subtypes (Ia, linked to chromosome 1 and Ib, linked to chromosome 17). Sporadic cases are very rare and the mutation rate, including both the subtypes, is estimated between 3 and 6 X 10(-6).

Charcot-Marie-Tooth Disease↗
PubMed1991

X-linked Charcot-Marie-Tooth disease. A linkage study in a large family by using 12 probes of the pericentromeric region.

Linkage analysis was performed on 41 subjects belonging to a large family with a recurrence of X-linked Charcot-Marie-Tooth disease (CMTX), by using 12 restriction fragment length polymorphism markers mapping in p11-q13. The results are in agreement with previous linkage data. Three new markers that are potentially useful for genetic analysis of CMTX families are described. A more precise estimate of the localization of the disease locus was attempted by multipoint linkage analysis.

Blotting, Southern↗
PubMed1991

Segregation and sporadic cases in families with Hunter's syndrome.

Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive disease, but the proportion of sporadic cases is significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples is apparent, but it is caused entirely by a sample of Ashkenazi families, whose segregation pattern has previously been interpreted as supporting the hypothesis of prenatal selection in favour of the pathological allele. Conversely, our joint analysis of the five samples by a maximum likelihood approach does not suggest segregation distortion. Possible reasons for the apparent lack of sporadic cases include the effect of ascertainment bias.

Alleles↗
PubMed1990

Segregation analysis of 1885 DMD families: significant departure from the expected proportion of sporadic cases.

The proportion of sporadic cases of Duchenne muscular dystrophy has been estimated by classical segregation analysis in a pooled sample of 1885 sibships from 7 different countries. A significant departure from the theoretical expectations based on mutation-selection equilibrium is observed (segregation frequency = 0.439 +/- 0.017; frequency of sporadic cases = 0.229 +/- 0.026, at the maximum likelihood). The occurrence of germinal mosaicism in some of the mothers of Duchenne cases may account for this peculiar finding, although a possible role of inequality of mutation rates in the two sexes cannot be ruled out.

Chromosomes, Human↗
PubMed1989

Problems in genetic counseling in a family with an "atypical" centronuclear myopathy.

Genetic counseling often deals with a rare disease the inheritance of which is not clearly established or in which genetic heterogeneity is reported. In addition, relevant parameters such as penetrance, gene frequency, and mutation rate may not be available. In this situation, establishing the risk may be very difficult. An example is presented in which Bayesian risk calculation proved to be of great help in providing precise risk estimates in a family in which an "atypical" centronuclear myopathy was segregating.

Adult↗
PubMed1987

Genetic epidemiology of myotonic dystrophy.

Prevalence rate of myotonic dystrophy (DM) was estimated in a large sample of the Italian population. Segregation analysis of the affected families suggests that subjects showing minor clinical signs, even in the absence of myotonic features, should be considered as bearers of the DM trait. An apparent excess of normal sibs among the offspring of DM subjects may be due to the late onset of the disease and possibly to a partial loss of affected individuals from the sample before diagnosis. Prevalence rate of DM in this study is estimated between 69 to 90 per million inhabitants; accordingly, DM might be the most frequent inherited neuromuscular disorder in human populations.

Adult↗