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Biomedical subjects

P Gallano

Publications and source records attributed to P Gallano.

At least 19 recordsLinked to original sources
PubMed2006

Dysferlin expression in monocytes: a source of mRNA for mutation analysis.

Dysferlin protein is expressed in peripheral blood monocytes. The genomic analysis of the DYSF gene has proved to be time consuming because it has 55 exons. We designed a mutational screening strategy based on cDNA from monocytes to find out whether the mutational analysis could be performed in mRNA from a source less invasive than the muscle biopsy. We studied 34 patients from 23 families diagnosed with dysferlinopathy. The diagnosis was based on clinical findings and on the absence of protein expression using either immunohistochemistry or Western blot of skeletal muscle and/or monocytes. We identified 28 different mutations, 13 of which were novel. The DYSF mutations in both alleles were found in 30 patients and only in one allele in four. The results were confirmed using genomic DNA in 26/34 patients. This is the first report to furnish evidence of reliable mutational analysis using monocytes cDNA and constitutes a good alternative to genomic DNA analysis.

DNA Mutational Analysis↗
PubMed2001

Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype.

We report a family with a new phenotype of autosomal recessive muscle dystrophy caused by a dysferlin mutation. The onset of the illness is distal, in the muscles of the anterior compartment group. The disease is rapidly progressive, leading to severe proximal weakness. Muscle biopsy showed moderate dystrophic changes with no vacuoles. Dysferlin immunostaining was negative. Gene analysis revealed a frameshift mutation in the exon 50 (delG5966) of the DYSF gene. This phenotype further demonstrates the clinical heterogeneity of the dysferlinopathies.

Adult↗
PubMed2000

Homogeneous phenotype of the gypsy limb-girdle MD with the gamma-sarcoglycan C283Y mutation.

OBJECTIVE: To characterize the clinical phenotype of LGMD2C in gypsies. BACKGROUND: Limb-girdle muscular dystrophy (LGMD) in gypsies of Western Europe is caused by a homozygous C283Y mutation on the same haplotype, suggesting a founder effect. METHODS: We performed clinical, laboratory, and muscle imaging studies of 40 patients. RESULTS: Mean age at onset was 5.3 years. One half of the patients had loss of ambulation by the age of 12; 13% still could walk after age 16. Calf hypertrophy, scapular winging, macroglossia, and lumbar hyperlordosis were common. Girdle, trunk, and proximal limb flexor muscles had earlier and more severe involvement. Cardiomyopathy was not observed. Five patients in the third decade of life required mechanical ventilation. Scoliosis was common in the nonambulatory stage. CONCLUSIONS: LGMD2C in gypsy patients with C283Y mutation presents a rather homogeneous phenotype, characterized by an initial Duchenne-like progressive course followed by a more prolonged survival rate possibly due to the absence of early respiratory impairment and cardiac failure.

Adolescent↗
PubMed1999

Novel mutations in the muscle chloride channel CLCN1 gene causing myotonia congenita in Spanish families.

Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, lead to recessive and dominant myotonia congenita. We report four novel mutations identified in this gene, after clinical, electromyographic, and genetic studies performed on 13 unrelated families. Two of the four mutations (2512insCTCA and A218T) were identified in families with Thomsen's disease, one (Q658X) in a family with Becker's disease, and the fourth (R669C) in a presumably sporadic patient with the Becker phenotype. Although identification of the mutations allows us to establish some genotype/phenotype correlations, this does not wholly account for the clinical heterogeneity and the inheritance patterns of the disease.

Chloride Channels↗
PubMed1999

Calpainopathy-a survey of mutations and polymorphisms.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized mainly by symmetrical and selective atrophy of the proximal limb muscles. It derives from defects in the human CAPN3 gene, which encodes the skeletal muscle-specific member of the calpain family. This report represents a compilation of the mutations and variants identified so far in this gene. To date, 97 distinct pathogenic calpain 3 mutations have been identified (4 nonsense mutations, 32 deletions/insertions, 8 splice-site mutations, and 53 missense mutations), 56 of which have not been described previously, together with 12 polymorphisms and 5 nonclassified variants. The mutations are distributed along the entire length of the CAPN3 gene. Thus far, most mutations identified represent private variants, although particular mutations have been found more frequently. Knowledge of the mutation spectrum occurring in the CAPN3 gene may contribute significantly to structure/function and pathogenesis studies. It may also help in the design of efficient mutation-screening strategies for calpainopathies.

Amino Acid Sequence↗
PubMed1998

[Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of dystrophin associated protein complex].

Linkage studies have confirmed the existence of clinical an genetic heterogeneity among the muscular dystrophies due to adhalin deficiency. We present the clinical, histological and genetic characteristics in a case of primary adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19 years-old woman, born of non consanguineous parents, who shows a long evolution myopathy with onset before age 7, a severe evolution and becoming wheelchair bound at 10 years. She showed evident calf pseudohypertrophy and serum creatinkinase (CK) levels were elevated (40-180 times the standard level). The histological pattern showed a destructed fascicular architecture in agreement with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal antibodies and abnormal staining pattern with anti-adhalin antibodies. The molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77 of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan complex localised in chromosome 17. In the light of this case, we suggest a revision of the diagnostic orientation in the muscular dystrophies and we review the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical signs which could indicate a given genetic locus.

Adult↗
PubMed1995

A novel insertional mutation of a single base on exon 12 of the dystrophin gene.

A new point mutation in exon 12 of the dystrophin gene was identified in a DMD patient using multiple SSCP analysis, which allows the simultaneous study of several exons. The mutation is an A insertion at position 1580 of the cDNA sequence, leading to a stop codon in the translational reading frame. This mutation was not observed in a sample of 70 DMD patients.

Adenine↗
PubMed1995

[Dystrophinopathies].

In 1987 a new concept in the X-linked muscular dystrophies was born with the identification of dystrophin, a cytoskeletal protein responsible for several muscular diseases previously grouped as Duchenne's or Becker's muscular dystrophies (DMD and BMD, respectively). Under the new concept these entities are referred to as dystrophinopathies. The discovery of dystrophin was made possible when polymerase chain reaction and reverse genetics opened the door to DNA examination. The DMD/BMD gene was located and sequenced and the protein product, dystrophin, was fully identified. The genetic study of dystrophinopathies was extended in the 1990's to include DNA analysis aimed at 1) discovering points of deletion or mutation that give rise to Xp21 myopathies, as dystrophinopathies are also known; 2) identifying the rules of protein translation (interruption or reading "signals" of the protein's genetic code), and 3) identifying atypical clinical phenotypes that can be diagnosed on a molecular level using anti-dystrophin antibodies or DNA probes.

Chromosome Aberrations↗
PubMed1994

Severe mental retardation in a young boy with an in-frame deletion in the dystrophin gene.

We report here a mentally retarded 32-month-old boy whose initial diagnosis was Angelman syndrome based on his clinical features. Cytogenetic studies showed a normal karyotype. Due to an elevated level of serum creatine kinase activity, we performed analyses to rule out a myopathic process. Although the electromyogram was normal, a few scattered necrotic fibres were seen in the muscle biopsy. DNA and dystrophin studies revealed an in-frame deletion in the 5' region of the dystrophin gene and an abnormal form of the protein product, consistent with a diagnosis of dystrophinopathy. We cannot totally rule out the possibility that this boy has the two separate conditions.

Child, Preschool↗
PubMed1989

Linkage disequilibrium for DNA haplotypes near the cystic fibrosis locus in two south European populations.

Three polymorphic DNA marker loci (INT1L1, D7S23 and D7S399) map to a chromosomal region that is very close to the cystic fibrosis (CF) locus in terms of genetic distance. These marker loci have been used to analyse the linkage disequilibrium in 137 CF families from two South European countries (Italy and Spain). The markers can be analysed for differences in linkage disequilibrium more easily in these populations than in North Europeans, in whom the disequilibrium between the allelic systems defined by the probes and CF is much greater and on a "plateau" through the genetic region. The different levels of disequilibrium found in the studied populations suggest that D7S399 and D7S23 are both closer to CF than INT1L1, and provide additional information on the origins and homogeneity of the CF defect.

Cystic Fibrosis↗
PubMed1989

Isolation of a new DNA marker in linkage disequilibrium with cystic fibrosis, situated between J3.11 (D7S8) and IRP.

A cosmid library of recombinants containing nonmethylated CpG sites for rare-cutter restriction enzymes was used previously to isolate the gene IRP and four polymorphic DNA markers (pPT-3, pXV-2c, pCS.7, and pKM.19) which are close to and in linkage disequilibrium with the cystic fibrosis (CF) mutation. We have analyzed several new clones from the same library and have isolated a further cosmid, cNX.6d, which maps approximately 160 kb from CS.7, in the J3.11 direction. A DNA fragment (pMP6d-9) (D7S399) derived from cosmid cNX.6d detects a frequent polymorphism with MspI. Strong linkage disequilibrium between CF and MP6d-9 is found in European populations. Recombinations in two families suggest that CF is between the MspI polymorphic site recognized by pMP6d-9 and the polymorphism recognized by pJ3.11. The new marker is the closest, to date, to CF and will be useful for prenatal diagnosis and carrier testing.

Chromosome Mapping↗
PubMed1989

[Use of dystrophin c-DNA for the direct diagnosis of Duchenne muscular dystrophy in female carriers].

DNA polymorphisms have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne Muscular Dystrophy (DMD) in affected families, but serious limitations are associated with this approach. The complementary DNA (c-ADN) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients. We present the study of five DMD families in which we have shown the existence of a partial deletion in the DMD gene in the affected boys. We have evaluated the usefulness of this direct approach to diagnose DMD carriers in these families using the c-DNA derived probes. In all cases we have obtained satisfactory results. The method seems to be more reliable, more rapid and less expensive than linkage studies with DNA polymorphisms.

Chromosome Deletion↗