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A Ballabio

Publications and source records attributed to A Ballabio.

At least 181 records · Page 10Linked to original sources
PubMed1989

Molecular heterogeneity of steroid sulfatase deficiency: a multicenter study on 57 unrelated patients, at DNA and protein levels.

Steroid sulfatase (STS) deficiency is the biochemical defect of X-linked ichthyosis (XLI), one of the most common X-linked disorders. We studied 57 European unrelated patients affected by STS deficiency. Twenty-eight patients were from Italy, 24 from the United Kingdom, 4 from The Netherlands, and 1 from Denmark. In two families XLI was associated with Kallmann syndrome (hypogonadotropic hypogonadism and anosmia). STS enzymatic activity was profoundly deficient in all cases. Direct DNA analysis, using cDNA and genomic probes from the STS gene and linked regions, demonstrated heterogeneity of the molecular defect. Forty-eight patients (84%) showed a deletion of the STS gene. In 44 cases the deletion also involved the STS flanking locus DXS237. In 1 patient a partial deletion of the STS gene was detected and in 9 patients no evidence of deletion was found. Locus DXS31 (probe M1A), previously mapped to Xp22.3-pter, was not deleted either in 24 patients with X-linked ichthyosis or in two families with X-linked ichthyosis associated with Kallmann syndrome. Consequently, the following loci order could be suggested: telomere--DXS31--(DXS237, STS)--Kallmann--centromere. Immunoblotting experiments, performed using anti-STS polyclonal antibodies, revealed the absence of cross-reacting material to STS in all cases tested, including 4 patients without evidence of deletions.

Arylsulfatases↗
PubMed1989

Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome.

Mendelian inherited disorders due to deletions of adjacent genes on a chromosome have been described as "contiguous gene syndromes." Short stature, chondrodysplasia punctata, mental retardation, steroid sulfatase deficiency, and Kallmann syndrome have been found as isolated entities or associated in various combinations in 27 patients with interstitial and terminal deletions involving the distal short arm of the X chromosome. The use of cDNA and genomic probes from the Xp22-pter region allowed us to identify 12 different deletion intervals and to confirm, and further refine, the chromosomal assignment of X-linked recessive chondrodysplasia punctata and Kallmann syndrome genes. A putative pseudoautosomal gene affecting height and an X-linked non-specific mental retardation gene have been tentatively assigned to specific intervals. The deletion panel described is a useful tool for mapping new sequences and orienting chromosome walks in the region.

Chromosome Deletion↗
PubMed1989

Molecular characterization of human X/Y translocations suggests their aetiology through aberrant exchange between homologous sequences on Xp and Yq.

Several DNA sequences from two homologous regions, localized on the distal part of the human X chromosome short arm and on the long arm of the Y chromosome, have been hybridized to DNAs from seven human-rodent hybrids containing human X; Y translocation chromosomes. Molecular characterization of the translocated chromosomes has revealed, in all but one case, transfer of the Y cluster of sequences and complete deletion of the corresponding X-chromosomal sequences. The possible role of X/Y homology in the aetiology of X; Y translocations is proposed.

Cell Line↗
PubMed1988

Ocular findings and skin histology in a group of patients with X-linked ichthyosis.

We carried out ophthalmological examinations, and histopathological examinations of skin biopsies in 32 male patients affected by X-linked ichthyosis. We found corneal opacities in only five patients, and their presence was not related to the age of the patients. Skin histology revealed a reduction of the granular layer in nine cases, a finding previously thought to be typical of autosomal dominant ichthyosis vulgaris.

Adolescent↗
PubMed1988

X/Y translocation in a family with X-linked ichthyosis, chondrodysplasia punctata, and mental retardation: DNA analysis reveals deletion of the steroid sulphatase gene and translocation of its Y pseudogene.

We describe a family with two male members showing an X/Y translocation (karyotype: 46,Y,der(X)t(X;Y)(p22;q11]. At physical examination both patients showed ichthyosis, mental retardation and dysmorphic features. Chondrodysplasia punctata and short stature were present in one case. Direct DNA analysis, using a steroid sulphatase cDNA probe, was performed in one patient, his mother and sister, both carriers of the translocation. We found that the translocated region of the Y chromosome includes the steroid sulphatase pseudogene. These results suggest that in our patients the X/Y translocation may be derived from a recombinational event between homologous regions located on the short arm of the X chromosome and the long arm of the Y chromosome. Clinical and molecular studies on the present family add further information for the construction of a tentative physical map of the distal Xp.

Child↗
PubMed1987

Sepsis score and acute-phase protein response as predictors of outcome in septic surgical patients.

In a series of 135 patients with severe surgical infections, we determined the sepsis score and the plasma level of the acute-phase proteins alpha-1-acid glycoprotein, alpha 1-antitrypsin, complement factor B, and C3. The initial sepsis score was a strong determinant of survival: in survivors it was significantly lower than in nonsurvivors. Only 8% of patients with a sepsis score above 20 survived. At the onset of severe sepsis, the plasma levels of all four acute-phase proteins were significantly lower in nonsurvivors. A significant elevation of C3a levels in the plasma of both surviving and nonsurviving patients indicated marked consumption of complement components in all patients with severe sepsis. A linear equation was developed to predict survival: sepsis index of survival (SIS) % = 121 + 0.26 (complement factor B) + 0.36 (alpha-1-acid glycoprotein)-6 (sepsis score). Based on our analysis, at the onset of severe sepsis, an SIS of 50% or more can correctly predict 88% of survivors and an SIS less than 50% can correctly predict 86% of nonsurvivors several days in advance of clinical outcome.

Adult↗
PubMed1987

Deletions of the steroid sulphatase gene in "classical" X-linked ichthyosis and in X-linked ichthyosis associated with Kallmann syndrome.

We have studied 16 men, from 10 unrelated Italian families, affected by steroid suphatase (STS) deficiency, which is the basic defect of X-linked ichthyosis (XLI). The patients' clinical diagnoses were of either isolated ichthyosis or ichthyosis associated with Kallmann syndrome (KS) (hypogonadotropic hypogonadism and anosmia). DNA from patients and their relatives was analysed by Southern blotting followed by hydridization with an STS cDNA probe. None of the patients affected by either XLI or XLI/KS showed any hybridization signal, thus revealing a deletion in the STS gene. We suggest that a gene deletion may be the most common molecular defect involved in XLI and that the syndrome XLI/KS may be due to a deletion of both the STS and the KS loci.

Chromosome Deletion↗
PubMed1987

Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis.

We have isolated several cDNA clones from a lambda gt11 expression library by screening with antibodies prepared against the microsomal enzyme steroid sulfatase, which is deficient in classical X-chromosome-linked ichthyosis patients. One of these clones (p422) has been assigned by mapping with a somatic cell hybrid panel and by in situ hybridization to Xp22.3. Clone p422 therefore has a coincident localization with the previously identified locus for steroid sulfatase expression in the region of the X chromosome escaping from inactivation. Twelve steroid sulfatase-deficient patients, including eight cases of classical ichthyosis, were found to be deleted for genomic sequences detected by the clone.

Chromosome Deletion↗
PubMed1987

Identification of incomplete coding sequences for steroid sulphatase on the human Y chromosome: evidence for an ancestral pseudoautosomal gene?

A cDNA clone (p422) containing about 200bp of coding sequences for steroid sulphatase (STS) has been isolated from a lambda gt11 expression library by antibody screening and has been assigned by mapping with a somatic cell hybrid panel and by in situ hybridization to Xp22.3; a localization coincident with the previously identified locus for STS expression. Although no significant hybridization of this clone to the Y chromosome was observed, p422 has been used to isolate a longer cDNA clone and genomic sequences which do recognize Y-specific restriction fragments. An abbreviated STS gene has been localized to Yq11.2. The coding sequences for the human enzyme shows little homology to sequences in mice.

Animals↗
PubMed1986

On the primary site of control in the spontaneous development of small-intestinal sucrase-isomaltase after birth.

We have compared the appearance in the small intestine of baby rabbits, of sucrase and isomaltase activities and of the sucrase-isomaltase mRNA. For the latter we used a cDNA probe encompassing approximately 4.1 kb from the 5'-end of pro-sucrase-isomaltase cDNA [(1986) Cell 46, 227-234]. Sucrase-isomaltase mRNA and the enzyme activities developed simultaneously from the 15th day after birth onwards. Over two orders of magnitude the enzymatic activities and sucrase-isomaltase mRNA matched one another closely, thus ruling out translation as the main site of biosynthetic control during spontaneous development, while rendering very probable transcription as the primary site of control. However, we cannot rule out the possibility that, prior to day 15, sucrase-isomaltase mRNA might be degraded so rapidly that it is not translated.

Age Factors↗
PubMed1986

X-linked ichthyosis, due to steroid sulphatase deficiency, associated with Kallmann syndrome (hypogonadotropic hypogonadism and anosmia): linkage relationships with Xg and cloned DNA sequences from the distal short arm of the X chromosome.

We report a large Italian pedigree in which five out of six males are affected by a syndrome, following an X-linked inheritance pattern, characterized by ichthyosis, hypogonadotropic hypogonadism, and anosmia. The concurrence of features of X-linked ichthyosis (XLI) with those of Kallmann syndrome, another disease often inherited as an X-linked trait, prompted us to perform biochemical, cytogenetic, and molecular studies in relation to the short arm of the X chromosome (Xp). Steroid sulphatase (STS) activity was found to be completely deficient in all affected members of the family. Prometaphase chromosome analyses of two obligate heterozygous women and one affected male showed normal karyotypes. Xg blood group antigen analysis and molecular studies employing cloned DNA sequences from the distal segment of the Xp (probes RC8, 782, dic56, and M1A), did not provide evidence for deletions or rearrangements of the X chromosome. The linkage analysis showed no crossovers between the disease, Xg, and DXS143, the locus defined by probe dic56, thus suggesting the possibility of a linkage between these two markers of the distal segment of Xp and the X-linked ichthyosis, hypogonadism, and anosmia syndrome.

Adolescent↗
PubMed1986

Genetics of Hunter syndrome: carrier detection, new mutations, segregation and linkage analysis.

We have investigated 31 families segregation for Hunter Syndrome in order to advance our understanding of the genetics of this disease. The hair root test for the diagnosis of carriers of Hunter Syndrome was improved by the adoption of a new diagnostic index that distinguishes between carrier and normal females better than previous methods of analysis. One hundred and eleven female relatives of the affected children were tested by such procedures. This showed that seven out of 31 mothers were not carriers (22.6%), thus suggesting a small deficit of new mutation relative to the expectation that 33% of lethal, recessive alleles arise anew in a population at equilibrium at a sex-linked locus with equal mutation rates in male and female gametogenesis. The difference, however, is not statistically significant. The age of the parents of new mutants was slightly but significantly raised. Nevertheless, the independent increase in the age of the fathers of new female mutants was not statistically significant. Finally, a deficit of affected males was observed. This was significant and suggests the possibility of intrauterine loss of some affected males. Linkage analysis between the Hunter Syndrome locus, three polymorphisms in the Factor IX gene and the anonymous polymorphic probes 52A and DX13 showed that the Hunter locus is fairly closely linked to DX13, and hence distal to the Factor IX gene, while no linkage was observed with the 52A polymorphic site. The maximum lod score for the linkage between factor IX and the Hunter Syndrome locus was 0.424 at theta = 0.25; and that for the linkage between the Hunter Syndrome locus and DX13 was 3.01 at theta = 0.1.

Age Factors↗
PubMed1986

Microtia with meatal atresia and conductive deafness: mild and severe manifestations within the same sibship.

Hereditary malformations of the external ear, such as microtia and meatal atresia, not associated with other congenital defects or syndromes, are rarely reported. Only a few familial cases have been described in which both dominant and recessive inheritance has been suggested. We report a sibship in which a wide variation of expression is present and recessive inheritance can be postulated.

Child↗
PubMed1985

Genetic complementation of steroid sulphatase after somatic cell hybridization of X-linked ichthyosis and multiple sulphatase deficiency.

Complementation studies of steroid sulphatase were carried out in the heterokaryon population of fibroblasts derived from patients with X-linked ichthyosis and multiple sulphatase deficiency. The activity of steroid sulphatase of the fused cell population was constantly higher (approximately 2-5 fold) than that of the unfused cocultivated cells. The occurrence of complementation further supports the hypothesis that at least two different loci control the expression of steroid sulphatase in the human genome.

Female↗