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Biomedical subjects

A Ballabio

Publications and source records attributed to A Ballabio.

At least 163 records · Page 9Linked to original sources
PubMed1992

[Non-malignant esophagotracheal fistulas in adults. Experience with 35 cases].

Esophagotracheal fistula always constitutes a serious, life-threatening complication. Fistulae occurring during medical intensive care with mechanical ventilation are currently the most frequent. Their diagnosis was strongly suspected by clinical examination of the patient, but was always confirmed by endoscopy which revealed their exact site in relation to the vocal cords or carina, essential information for the choice of incision when it is decided to perform surgery. Twenty-five patients were treated medically. Treatment was always combined with gastrointestinal resting, control of gastro-oesophageal reflux and broad-spectrum systemic antibiotics. There were 19 deaths and 6 fistulae closed spontaneously. Three of these 6 patients developed a secondary tracheal stenosis, 2 of which were treated surgically by resection-anastomosis. Ten fistulae were closed surgically with a good long-term result. The indication for surgery was essentially based on the patients general and infectious status and on his or her respiratory autonomy. Technically, we always combined direct suture of the two organs with interposition of muscular or pleural tissue.

Adult↗
PubMed1992

Identification of point mutations in the steroid sulfatase gene of three patients with X-linked ichthyosis.

X-linked ichthyosis (XLI) is an inborn error of metabolism caused by steroid sulfatase (STS) deficiency. In more than 80% of XLI patients the enzyme deficiency is due to large deletions involving the entire STS gene and flanking sequences. However, some patients with the classical XLI phenotype and complete STS deficiency do not show any detectable deletions by Southern blot analysis using full-length STS cDNA as a probe. We have studied five unrelated patients who are such "nondeletion" mutants. Western blot analysis using anti-STS antibodies was performed on patients' fibroblast extracts and revealed absence of cross-reacting material. First-strand cDNA synthesis by reverse transcription from patients' RNA isolated from cultured fibroblasts and PCR amplification of overlapping segments of the entire STS polypeptide coding region were performed. Three point mutations were identified by chemical mismatch cleavage, sequenced by dideoxynucleotide chain-termination sequencing and confirmed by allele-specific oligonucleotide hybridization of the patients' genomic DNA. The mutations resulted in the substitution of a tryptophan for an arginine at codon 1319, changing a hydrophobic to a basic hydrophilic amino acid, the substitution of a cysteine for a tyrosine at codon 1542, potentially losing a disulfide bond, and the substitution of a serine for a leucine at codon 1237. These are the first point mutations to be documented in the STS gene and may allow insight into functionally important domains of the protein.

Amino Acids↗
PubMed1991

Deletion of the distal short arm of the X chromosome (Xp) in a patient with short stature, chondrodysplasia punctata, and X-linked ichthyosis due to steroid sulfatase deficiency.

We observed a boy with short stature, chondrodysplasia punctata, ichthyosis, and a terminal deletion of Xp. Steroid sulfatase deficiency was demonstrated in the patient's fibroblasts. Molecular analysis showed a deletion of the entire steroid sulfatase gene. This case represents another example of a contiguous gene syndrome in which the co-deletion of adjacent genes on a chromosome is responsible for a complex phenotype.

Abnormalities, Multiple↗
PubMed1991

A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules.

Kallmann's syndrome (clinically characterized by hypogonadotropic hypogonadism and inability to smell) is caused by a defect in the migration of olfactory neurons, and neurons producing hypothalamic gonadotropin-releasing hormone. A gene has now been isolated from the critical region on Xp22.3 to which the syndrome locus has been assigned: this gene escapes X inactivation, has a homologue on the Y chromosome, and shows an unusual pattern of conservation across species. The predicted protein has significant similarities with proteins involved in neural cell adhesion and axonal pathfinding, as well as with protein kinases and phosphatases, which suggests that this gene could have a specific role in neuronal migration.

Base Sequence↗
PubMed1991

Alu-primed polymerase chain reaction for regional assignment of 110 yeast artificial chromosome clones from the human X chromosome: identification of clones associated with a disease locus.

Over 400 yeast artificial chromosome (YAC) clones were isolated from the human X chromosome, and 110 of these were assigned to regions defined by chromosome translocation and deletion breakpoints. Polymerase chain reaction using Alu primers was applied to YAC clones in order to generate probes, to identify overlapping clones, and to derive "fingerprints" and sequence data directly from total yeast DNA. Several clones were identified in regions of medical interest. One set of three overlapping clones was found to cross a chromosomal translocation implicated in Lowe syndrome. The regional assignment of groups of YAC clones provides initiation points for further attempts to develop large cloned contiguous sequences, as well as material for investigation of regions involved in genetic diseases.

Base Sequence↗
PubMed1991

Characterization of a murine gene expressed from the inactive X chromosome.

In mammals, equal dosage of gene products encoded by the X chromosome in male and female cells is achieved by X inactivation. Although X-chromosome inactivation represents the most extensive example known of long range cis gene regulation, the mechanism by which thousands of genes on only one of a pair of identical chromosomes are turned off is poorly understood. We have recently identified a human gene (XIST) exclusively expressed from the inactive X chromosome. Here we report the isolation and characterization of its murine homologue (Xist) which localizes to the mouse X inactivation centre region and is the first murine gene found to be expressed from the inactive X chromosome. Nucleotide sequence analysis indicates that Xist may be associated with a protein product. The similar map positions and expression patterns for Xist in mouse and man suggest that this gene may have a role in X inactivation.

Amino Acid Sequence↗
PubMed1991

A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome.

X-chromosome inactivation results in the cis-limited dosage compensation of genes on one of the pair of X chromosomes in mammalian females. Although most X-linked genes are believed to be subject to inactivation, several are known to be expressed from both active and inactive X chromosomes. Here we describe an X-linked gene with a novel expression pattern--transcripts are detected only from the inactive X chromosome (Xi) and not from the active X chromosome (Xa). This gene, called XIST (for Xi-specific transcripts), is a candidate for a gene either involved in or uniquely influenced by the process of X inactivation.

Base Sequence↗
PubMed1991

Localization of the X inactivation centre on the human X chromosome in Xq13.

X-chromosome inactivation results in the strictly cis-limited inactivation of many but not all genes on one of the two X chromosomes during early development in somatic cells of mammalian females. One feature of virtually all models of X inactivation is the existence of an X-inactivation centre (XIC) required in cis for inactivation to occur. This concept predicts that all structurally abnormal X chromosomes capable of being inactivated have in common a defineable region of the X chromosome. Here we report an analysis of several such rearranged human X chromosomes and define a minimal region of overlap. The results are consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing the XIC region. One of the markers that defines this region is the XIST gene, which is expressed specifically from inactive, but not active, X chromosomes. The localization of the XIST gene to the XIC region on the human X chromosome implicates XIST in some aspect of X inactivation.

Chromosome Mapping↗
PubMed1991

Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater.

Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study. The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score. A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%). Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls. The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.

Adolescent↗
PubMed1991

A deletion map of the human Yq11 region: implications for the evolution of the Y chromosome and tentative mapping of a locus involved in spermatogenesis.

A deletion map of Yq11 has been constructed by analyzing 23 individuals bearing structural abnormalities (isochromosomes, terminal deletions and X;Y, Y;X, or A;Y translocations) in the long arm of the Y chromosome. Twenty-two Yq-specific loci were detected using 14 DNA probes, ordered in 11 deletion intervals, and correlated with the cytogenetic map of the chromosome. The breakpoints of seven translocations involving Xp22 and Yq11 were mapped. The results obtained from at least five translocations suggest that these abnormal chromosomes may result from aberrant interchanges between X-Y homologous regions. The use of probes detecting Yq11 and Xp22.3 homologous sequences allowed us to compare the order of loci within these two chromosomal regions. The data suggest that at least three physically and temporary distinct rearrangements (pericentric inversion of pseudoautosomal sequences and/or X-Y transpositions and duplications) have occurred during evolution and account for the present organization of this region of the human Y chromosome. The correlation between the patient' phenotypes and the extent of their Yq11 deletions permits the tentative assignment of a locus involved in human spermatogenesis to a specific interval within Yq11.23.

Adolescent↗
PubMed1991

Contiguous deletion syndromes.

In the past few years, clinical, cytogenetic and molecular analysis of patients with complex phenotypes has led to the identification of syndromes caused by deletions of adjacent disease genes on a chromosome. These conditions, referred to as contiguous deletion syndromes, are an important component of the syndromes recognized in medical genetics, and the DNA from patients affected by these disorders is useful for the mapping and cloning of disease genes.

Chromosome Aberrations↗
PubMed1990

Screening for steroid sulfatase (STS) gene deletions by multiplex DNA amplification.

Deletions are the most common molecular defect in steroid sulfatase (STS) deficiency. We describe the application of multiplex DNA amplification, by polymerase chain reaction, for deletion screening in patients with STS deficiency (STS-PCR). Genomic DNA from 38 unrelated patients was amplified using two sets of primers, corresponding to the 5' and the 3' ends of the STS gene. The analysis of the amplified products was always consistent with the results obtained by Southern analysis. This method represents a sensitive fast non-radioactive test for detecting STS gene deletions.

Arylsulfatases↗
PubMed1990

Two families of low-copy-number repeats are interspersed on Xp22.3: implications for the high frequency of deletions in this region.

The locations of two families of low-copy-number repeats (CRI-S232 and G1.3) in the physical and genetic maps of the distal short arm of the human X chromosome (Xp22.3) have been determined. Single-copy fragments flanking several repeat elements from each family have been cloned and assigned to specific intervals on a deletion map of Xp22.3. Physical distances between these loci and previously isolated Xp22.3 markers have been determined by pulsed-field gel electrophoresis (PFGE). The positions of some of these markers on the genetic map of the region have been established by segregation analysis in CEPH families. Four members of the CRI-S232 family have been localized within 3 Mb on Xp22.3, interspersed with two members of the G1.3 family. Both deletion and PFGE mapping data suggest that a CpG island localized in a specific position on the map might be associated with the Kallmann syndrome gene. Unlike the previously reported data on hyperpolymorphic minisatellite sequences, no increase in the recombination rate was detected around the CRI-S233 repeats. The presence of several repeat elements in a region with a very high frequency of deletions, such as Xp22.3, is highly suggestive of the occurrence of unequal crossovers between the various elements, leading to deletion events.

Chromosome Deletion↗
PubMed1990

Long-range physical mapping around the human steroid sulfatase locus.

The region of the human X chromosome containing the steroid sulfatase locus was analyzed by pulsed-field gel electrophoresis. Restriction site maps were generated for the X chromosome in the blood of a normal male individual and that in the mouse-human hybrid cell line ThyB-X; these maps extend over approximately 4.3 Mb of DNA of the former, and 3.2 Mb of the latter. Physical linkage was defined between the STS locus and sequences detected by the probes GMGX9 (DXS237), GMGXY19 (DYS74), CRI-S232 (DXS278), and dic56 (DXS143), and the order telomere--(STS, DYS74)--DXS237--DXS278--DXS143--centromere was deduced. The pulsed-field maps were used to demonstrate a deletion of 180 kb of DNA from the X chromosome of an individual with X-linked ichthyosis. Also, possible locations for the Kallmann syndrome gene were revealed, and the distance between the steroid sulfatase locus and the pseudoautosomal region was estimated to be at least 4 Mb.

Animals↗
PubMed1990

Definitive localization of X-linked Kallman syndrome (hypogonadotropic hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-S232.

Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism and anosmia. Six families in which the disorder followed an X-linked inheritance were investigated by linkage analysis. Diagnostic criteria were uniformly applied and included tests for hypogonadotropic hypogonadism and anosmia. Close linkage was found by using the hypervariable repeated sequence CRI-S232 (DXS278) previously mapped to Xp22.3. At a maximum lod score of 6.5, the recombination fraction was calculated as .03. Of 30 fully informative meioses, one recombination between the disease locus and the loci recognized by probe CRI-S232 was observed. When an independent approach is used, these results confirm the X-linked Kallmann syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome to the Xp22.3 region. This opens the way to carrier detection and to the identification of a gene responsible for this disorder.

Chromosome Mapping↗