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

Ballabio, Andrea; Carrozzo, Romeo; Parenti, Giancarlo; Gil, Angel Martı́nez; Zollo, Massimo; Persico, M. Graziella; Gillard, E.F.; Affara, Nabeel A.; Yates, John R.; Ferguson‐Smith, M. A.; Frants, R.R.; Eriksson, Aldur W.; Andria, Generoso

doi:10.1016/0888-7543(89)90311-x

Cited by 98 publications

(77 citation statements)

References 14 publications

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“…A total of 102 STS-deficient patients has been studied collectively and only 13 patients' DNA contains all or part of the STS X chromosome-encoded sequences. The results in 57 of these patients were inconclusive because their DNAs were studied with incomplete cDNA fragments (3,5,7), which would score a partial deletion either positive or negative depending on the sizes and locations of the deletions. In the two studies using nearly full-length cDNA (refs.…”

Section: Discussionmentioning

confidence: 99%

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Molecular studies of deletions at the human steroid sulfatase locus.

Shapiro

Yen

Pomerantz

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

108

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The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment ofDNA that is unique to the X chromosome. In contrast to most X chromosomeencoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS (steryl-sulfatase; steryl-sulfate sulfohydrolase, EC 3.1.6.2) activity produces the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS-individuals have large deletions at the STS locus. We and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome.

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Section: Discussionmentioning

confidence: 99%

“…Such individuals are thought to have extensive deletions of their X chromosomes, which could produce contiguous gene loss. In support of this concept, =90% of patients with simple deficiency of STS and isolated ichthyosis appear to have molecular evidence of deletion of some or all of their STS gene sequences (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 91%

Molecular studies of deletions at the human steroid sulfatase locus.

Shapiro

Yen

Pomerantz

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

108

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“…In our study, PCR analysis on the patients revealed an interstitial deletion with the telomeric breakpoint located between DXS996 and DXS1139, and the centromeric breakpoint located between DXF22S1 and DXS278. Ballabio et al (21), Saeki et al (22), Jimenez Vaca et al (23) and Aviram-Goldring et al (24) demonstrated the molecular heterogeneity of the STS deficiency in their studies of XLI patients of various races. Their results revealed heterogeneity in the deletion pattern among all patients with XLI.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of a 12-year-old boy with X-linked ichthyosis in association with sclerosing glomerulonephritis

Song

Chen

et al. 2013

Molecular Medicine Reports

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Abstract. In this study, we report the case of a 12-year-old male with X-linked ichthyosis (XLI) in association with glomerular sclerosis, and our investigation into the deletion pattern of the STS gene and the flanking regions in DNA samples of family members. We observed no features typical of renal osteodystrophy or rickets, with the exception of short stature, in the three afffected male family members. Audiometry, visual acuity and olfactory sensation were normal. By performing PCR analysis of the steroid sulfatase (STS) gene and flanking regions on our patients, we discovered a complete deletion that involved the entire region from DXS1139 to DXF22S1. Further studies are required to determine whether the STS gene or the co-deleted flanking sequences are the cause of renal disease associated with XLI. IntroductionX-linked ichthyosis (XLI; OMIM #308100) is an inherited metabolic disorder resulting from a steroid sulfatase (STS) deficiency (1). It affects ~1:2,000-6,000 males, with little racial or geographic variation (2-4). Of the males affected, >90% manifest with generalized exfoliation of the skin within a few weeks of being born. Later, they develop large, polygonal, dark-brown scales symmetrically distributed over the extremities, trunk and neck, but typically sparing the face, palms and soles. The skin lesions persist throughout the life of the patient. Extracutaneous manifestations are common, particularly with corneal opacities and cryptorchidism (4). Other associated features, although extremely rare, include mental retardation, epilepsy, pyloric hypertrophy, congenital defects of the abdominal wall and acute lymphoblastic leukemia (3,5).For the majority of affected males (90%), XLI is caused by a STS deficiency due to the complete deletion of the STS gene located on the short arm of the X chromosome (Xp22.3). The remaining 10% of males demonstrate a point mutation or partial deletion (4,6,7). Larger deletions involving neighboring genes (contiguous gene deletion syndromes) may result in XLI associated with Kallman syndrome (KS) or X-linked recessive chondrodysplasia punctata (CDXP) (4,6,7).In this study, we report on the case of a 12-year-old male with XLI in association with glomerular sclerosis. Ichthyosis also affects two other members of the patient's family. The case report describes our investigation into the deletion pattern of the STS gene and flanking regions in DNA samples of the family members. The study was approved by the Ethics Committee of The Second Xiangya Hospital of Central South University, Changsha, Hunan, China and consent was obtained from the the patient's family Case reportPatient history. A 12-year-old male presented with increasing nocturnal urine volume for five years, pallor for one year and discontinuous tetany for the previous two days. At seven years old, the increase in urine volume, ~800 ml/night, in addition to enuresis were noted, but aggravated gradually. There was no history of oliguria or edema. The patient was the product of a non-consanguineous marriage and...

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“…308100) provides a well-characterized example of pathology caused by duplications at some distance from one another. This disease was mapped to Xp22.32, and ∼90% of ichthyosis patients were found to be deleted for the entire steroid sulfatase gene (Ballabio et al 1989;Shapiro et al 1989). Molecular analysis of the region revealed four homologous sequence elements, one distal and three proximal to steroid sulfatase (STS), distributed over 2.5 Mb.…”

Section: X-linked Clusters and Pathologymentioning

confidence: 99%

Pathological Consequences of Sequence Duplications in the Human Genome

Mazzarella

Schlessinger²

1998

Genome Res.

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As large-scale sequencing accumulates momentum, an increasing number of instances are being revealed in which genes or other relatively rare sequences are duplicated, either in tandem or at nearby locations. Such duplications are a source of considerable polymorphism in populations, and also increase the evolutionary possibilities for the coregulation of juxtaposed sequences. As a further consequence, they promote inversions and deletions that are responsible for significant inherited pathology. Here we review known examples of genomic duplications present on the human X chromosome and autosomes.

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

Cited by 98 publications

References 14 publications

Molecular studies of deletions at the human steroid sulfatase locus.

Molecular studies of deletions at the human steroid sulfatase locus.

Genetic analysis of a 12-year-old boy with X-linked ichthyosis in association with sclerosing glomerulonephritis

Pathological Consequences of Sequence Duplications in the Human Genome

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