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P Gallano

Publications and source records attributed to P Gallano.

32 records · Page 2Linked to original sources
PubMed1987

[Molecular diagnosis of Duchenne and Becker muscular dystrophies. Current data].

Carrier diagnosis and prenatal diagnosis of Duchenne's muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) has become possible using some twenty RFLPs detected by more than a dozen Xp21 probes that are either intragenic or flanking the disease locus. Results from familial studies on 88 DMD and BM families stress important considerations concerning a priori and final risks, individuals necessary for the identification of the phase, and the different strategies that can be applied, regardless of whether the study concerns an on-going pregnancy or a carrier-status determination, and whether the patient is at high or low risk. Finally, multiple sources of difficulties in interpreting the results depend on a) the occurrence of new mutations that must be traced; b) the existence of meiotic recombination; c) the necessity, in some instances, of relying upon the sole identification of the paternal X. These considerations emphasize the characteristics and the important limitations of this type of methodology.

Creatine Kinase↗
PubMed1986

The pro alpha 2(V) collagen gene (COL5A2) maps to 2q14----2q32, syntenic to the pro alpha 1 (III) collagen locus (COL3A1).

A recombinant probe specific for the pro alpha 2 chain of human Type V collagen has been used for the localization of the corresponding gene (COL5A2) to chromosome 2. Regional mapping by in situ hybridization and analysis of DNA from human X rodent cell lines indicated that COL5A2 is confined within the segment 2q14----2q32, thus syntenic to the pro alpha 1 (III) collagen gene (COL3A1).

Animals↗
PubMed1986

Segregation analysis of balanced pericentric inversions in pedigree data.

The results of the recent European collaborative prenatal study suggested a segregation distortion of balanced pericentric inversions from carrier fathers but not carrier mothers (Boué & Gallano 1984). In an attempt to confirm these unexpected results, we examined 216 pedigrees with balanced pericentric inversions collected from three centers and from the literature. We were unable to detect any significant deviation from the expected 1:1 segregation of balanced pericentric inversions to normal karyotypes among the offspring of either carrier parent. To clarify the discrepancy between the studies, we reanalyzed the data from the prenatal study using all karyotyped individuals and, assuming conventional ascertainment rules, found a normal segregation pattern. We conclude that balanced pericentric inversions segregate normally in both males and females and that some retrospectively selected pedigrees were included as prospective in the prenatal study and this misclassification caused the apparent segregation distortion from carrier fathers.

Chromosome Inversion↗
PubMed1985

The organization of two related subfamilies of a human tandemly repeated DNA is chromosome specific.

Several clones containing clusters of repetitive elements were isolated from a human chromosome 22 specific library. An EcoRI-XhoI fragment of 860bp was subcloned and was shown to belong to a family of tandemly repeated DNA linked to the Y-specific 3.4 kb HaeIII band. This probe hybridizes to several sets of sequences or subfamilies. The most abundant subfamily is a 1.8kb long sequence containing one EcoRV site, and in most repeats, one AvaII and one KpnI site. Using human-rodent somatic cell hybrid DNA, we have shown that this cluster is present on human chromosome 9 although presence on chromosome 15 is not excluded. Another subfamily, 6.1kb long, appears to be exclusive of chromosome 16. By in situ hybridization with metaphasic chromosomes, these sets of repeats were mapped to the constitutive heterochromatin of a few chromosomes. Coexistence in one genome of long tandem repeats of distinct organization but similar length may represent the outcome of a continuous process of fixation of variant sequences. Homologous repeats are also abundant in four higher primate genomes (Orangutan, gorilla, chimpanzee, and man) but absent in other primates (African green monkey, rhesus monkey, baboon, and mouse lemur).

Animals↗
PubMed1985

The structural gene for aldolase B (ALDB) maps to 9q13----32.

We used a cloned cDNA probe for the B subunit of human aldolase (ALDB) and Southern blotting techniques to analyse DNA from a series of rodent X human somatic cell hybrids for the presence of specific ALDB-related sequences. Our results provide evidence for the assignment of the gene for ALDB to chromosome 9. Moreover, by direct gene dosage determination in two patients with chromosome 9 unbalanced rearrangements and by in situ hybridization we refined the regional chromosomal assignment to 9q13----q32 and most probably to 9q21.3----9q22.2.

Animals↗
PubMed1984

A collaborative study of the segregation of inherited chromosome structural rearrangements in 1356 prenatal diagnoses.

A collaborative study involving 71 European prenatal diagnosis centres has collected 1356 observations on the karyotype of fetal cells in diagnoses performed in couples in which a parent had a balanced structural rearrangement. The segregations of the inherited chromosome structural rearrangement were analysed in relation to the types of rearrangement, to the sex of the carrier parent, the methods of ascertainment of the anomaly in the family, the chromosomes involved and the potential imbalance of the anomaly. Wide differences in the incidence of unbalanced fetuses were observed in relation to these criteria, and these results can be used in counselling parents with balanced rearrangements. Distortions in segregation of normal versus balanced karyotypes were observed in some types of anomalies.

Chromosome Aberrations↗
PubMed1983

Lambda Ig constant region genes are translocated to chromosome 8 in Burkitt's lymphoma with t(8;22).

By in situ hybridization of normal human chromosomes with a cloned genomic probe specific for the constant region of the lambda immunoglobulin genes, band 22q11 was preferentially labelled. In two cell lines with t(8;22) derived from Burkitt's lymphoma a strong signal was noted on the 8q+ chromosome derivative, indicating that the constant region of the lambda Ig gene cluster was translocated from chromosome 22 to chromosome 8. In addition, the signal observed on the 22q- derivative chromosome was stronger than the background in one of the two cell lines tested, but not in the other. The implications are that the break point in chromosome 22 in some cases lies within the Ig gene itself or between clusters of such genes, and that different cases have different break points.

Burkitt Lymphoma↗
PubMedDate not supplied

Prospective risk in reciprocal translocation heterozygotes at amniocentesis as determined by potential chromosome imbalance sizes. Data of the European Collaborative Prenatal Diagnosis Centres.

The Date of the European Cooperative Prenatal Diagnosis Laboratories (Boué and Gallano, 1984) of 596 prenatal (amniocyte) diagnoses of familial rcp was examined as to relationships between balanced/unbalanced result and ascertainment, carrier parent and chromosome imbalance size (percentage haploid autosome length). Each rearrangement was graphed once with actual (unbalanced result) or potential (normal or balanced result) imbalances plotted with trisomy as the ordinate and monosomy as the abscissa. The graphed data was divided into 15 regions, each of 2.0 per cent trisomy and 0.75 per cent monosomy and the rate of unbalanced pregnancies determined for each region. The highest rates of chromosomally unbalanced progeny (excluding regions with inadequate data) were found closest to the origin (i.e. associated with the smallest imbalances) and these were for ascertainment category 1 (previous rcp unbalanced child) 22.3 per cent for maternal carriers and 39 per cent for paternal carriers. Overall in pooled data for this ascertainment category (without reference to the imbalance graphs) there were for paternal carriers 28.6 per cent unbalanced pregnancies and for maternal carriers 18.1 per cent. The graphed data, therefore, revealed the higher rates associated with some of the rcp with small potential (combined duplication/deficiency) imbalances. Lesser rates were observed for ascertainment category 2 (carrier parent with a history of recurrent miscarriage) with overall percentages of imbalanced progeny ranging from 2.7 (paternal carriers) to 4.7 (maternal carriers). Again, higher rates were revealed in graphed data for small potential imbalances. All unbalanced results for this group (ascertainment category 2) plotted in the region closest to the origin with rates of 16 per cent (maternal carriers) and 9.5 per cent (paternal carriers) in this region. Remarkably in both ascertainment groups 1 and 2 there was no significant difference in the size of the imbalanced segments for unbalanced progeny. In ascertainment group 1 this was (dup/def; mean +/- S.D.): 1.09 +/- 0.77/0.47 +/- 0.45 and in ascertainment group 2: 1.09 +/- 0.80/0.66 +/- 0.71. From the graphed data which arguably denote viability relationships, a trisomy was approximately 2.7 times as likely to survive until amniocentesis as a monosomy of equivalent size. It is proposed that given further data, risk estimates could be determined for rcp heterozygotes using the present approach where empiric data (from the family history or an analysed series of similar rcp) is not available.

Chromosome Aberrations↗
PubMedDate not supplied

Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder for which the biochemical defect is as yet unknown. Recently, two cloned segments of human X-chromosome DNA have been described which detect structural alterations within or near the genetic locus responsible for the disorder. Both of these cloned segments were described as tightly linked to the locus and were capable of detecting deletions in the DNA of boys affected with DMD. In an attempt to determine more precisely the occurrence of these deletions within a large population of DMD patients and the accuracy of one of the segments, DXS164 (pERT87), in determining the inheritance of the DMD X chromosome, the subclones 1, 8 and 15 were made available to many investigators throughout the world. Here we describe the combined results of more than 20 research laboratories with respect to the occurrence of deletions at the DXS164 locus in DNA samples isolated from patients with DMD and Becker muscular dystrophy (BMD). The results indicate that the DXS164 locus apparently recombines with DMD 5% of the time, but is probably located between independent sites of mutation which yield DMD. The breakpoints of some deletions are delineated within the DXS164 locus, and it is evident that the deletions at the DMD locus are frequent and extremely large.

Chromosome Deletion↗
PubMedDate not supplied

Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a founder mutation in the gamma-sarcoglycan gene.

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with primary gamma-sarcoglycan deficiency, generally associated with a severe clinical course. gamma-sarcoglycan, a 35kDa dystrophin-associated protein, is encoded by a single gene on chromosome 13q12. Six different mutations have been described in that gene, and it has been proved they are the origin of the disease. One of these mutations (C283Y), a G-->A transition in codon 283, was recently and exclusively identified in Gypsy patients from different European countries. We report the study of 11 LGMD2C unrelated Gypsy families (nine Spanish and two Portugese). The muscle biopsies of these patients showed a drastically decreased immunostaining with alpha and gamma-sarcoglycan antibodies. All the patients were homozygous for C283Y missense mutation, and all affected chromosomes (patients and heterozygous relatives) carried the allele 5 (112 bp) of the intragenic microsatellite D13S232. Unexpectedly, this allele is most frequent in the Caucasian population but not in the normal Gypsy population. The clinical severity of all patients demonstrates that the C283Y missense mutation in a homozygous state causes a severe LGMD2C (DMD-like). The elevated number of families ascertained let us assume that LGMD2C is prevalent in the Gypsy population, and that all the families have inherited a founding mutation.

Consanguinity↗
PubMedDate not supplied

[Alterations in functional proteins. Calpaine-3 deficiency].

INTRODUCTION: Muscular dystrophies due to calpain deficiency are the first example of a muscular dystrophy due to the mutation of a gene codifying for a non-structural enzymatic protein of unknown function and substrate. DEVELOPMENT: More than 70 mutations have been described in the gene structure, localized to chromosome 15. Although the time course and topography is fairly homogeneous, correlation between the different mutations and the phenotype has still to be analyzed. The age of onset of symptoms is usually between 8 and 14, with no difference between the sexes. There is a slow but uniformly progressive course starting in the pelvis and extending to the shoulder and the distal musculature. Almost all patients are confined to a wheelchair twenty years after onset of the disease. There is no facial, oculomotor or bulbar involvement and gemellar pseudohypertrophy is rare. However, a winged scapula and marked lumbar hyperlordosis is universal. No cardiac or cognitive changes have been observed. Muscle CT shows a pattern of atrophy, mainly of the posterior and medial muscle compartments and of the posterosuperficial group of the legs, which varies depending on the time the disorder has been present. This condition is the commonest etiological group of the dystrophy syndromes, especially of those of late infancy or juvenile onset, in the open populations studied to date. Muscle biopsy, stained by all methods available, is essential to rule out other types of progressive dystrophies secondary to deficiencies of structural proteins.

Adult↗
PubMedDate not supplied

[Early onset adhalinopathy (LGMD2D) mimicking congenital muscular dystrophy].

INTRODUCTION: The recent discovery of the dystrophin-associated complex of glycoproteins led to the delineation of sarcoglycanopathies, a phenotypically similar to dystrophinopathies group of clinically heterogeneous and progressive muscular dystrophies. The objective of this paper is to report the clinical, biochemical, histological, immunohistochemical and molecular genetics characteristics observed in a case of adhalinopathy (alpha-sarcoglycanopathy or LGMD2D) presenting in early months of life and resembling congenital muscular dystrophy. CLINICAL CASE: An 12-year old school boy, the third son of a healthy, young, non consanguineous couple, presented at birth with bilateral cleft lip, cleft palate and mild hypotonia. At age 6 months it was believed he suffered from a benign form of congenital muscular dystrophy on the basis of clinical, biochemical, electrophysiological and histological findings. From 5 years onwards he had frequent falls and climbing stairs had become increasingly difficult. Also, a positive Gowers 'sign, mild calf hypertrophy, high serum creatine-phosphokinase level and myopathic electromyographic features were present; otherwise, cardiological evaluation and intelligence were normal. A repeated muscular biopsy at 10 years showed dystrophic features as well as selective deficiency of adhalin on immunostaining. DNA analysis demonstrated the patient being homozygote for a R77C mutation. Actually, a marked lumbar lordosis and waddling gait, an impossibility of climbing stairs and arising from the floor in addition to absent rotulian reflexes and mild Achilles retraction are present. CONCLUSIONS: LGMD2D may present in the first months of life mimicking congenital muscular dystrophy. It seems reasonable that biopsies of all new cases of muscular dystrophies be selectively immohistochemical analyzed, and when it is possible the diagnosis should be confirmed by DNA analysis.

Biomarkers↗
PubMedDate not supplied

[Muscular dystrophy due to a deficit of gamma-sarcoglycan. A report of three patients with the Delta-521t mutation].

INTRODUCTION: gamma-sarcoglicanopathies, also classified as limb girdle muscular dystrophy type 2C (LGMD2C) are a group of autosomal recessive muscular dystrophies due to mutations in 13q12 and subsequent g sarcoglican deficiency. The protein is one of the components of the dystrophin associated glycoprotein complex and is thought to impart structural integrity to the myofibre. The clinical course of the disease may be heterogeneous, ranging from severe forms with onset in the first decade and rapid progression resembling Progressive Duchenne muscular dystrophy (DMD) to milder forms with later onset and slower course. Cases hitherto reported in Spain corresponds to gypsie patients, homozygous for C283Y missense mutation. CASE REPORTS: Here, we report three new galician (Northwest Spain) patients (one male and one female sibling cases) with a severe DMD like muscular dystrophy homozygous for D 521T. In the first male familial case, initial diagnosis of DMD was made. On reevaluation fourteen years later, inmunohistochemical and molecular studies allowed for a definitive g sarcoglicanopathy diagnosis. CONCLUSIONS: Patients with a primary sarcoglycanopathy may be clinically indistinguishable from those with the primary dystrophinopathies. Probably, the diagnosis of LGMD are underestimated and a number of male patients diagnosed as DMD really corresponds to a recessive form o muscular dystrophy. Consequently, a definitive diagnosis rests on appropriate inmunohistochemical and molecular analysis, specially in those patients showing a normal pattern of dystrophin and/or suggestive for an autosomal recessive mode of inheritance.

Adolescent↗