Abstract:
: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.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Basler E,Grompe M,Parenti G,Yates J,Ballabio Asubject
Has Abstractpub_date
1992-03-01 00:00:00pages
483-91issue
3eissn
0002-9297issn
1537-6605journal_volume
50pub_type
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/505406
更新日期:2006-07-01 00:00:00
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journal_title:American journal of human genetics
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doi:10.1016/j.ajhg.2015.09.010
更新日期:2015-11-05 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/522890
更新日期:2007-11-01 00:00:00
abstract::Cloned genomic DNA sequences corresponding to various regions of the human type II procollagen gene were used to analyze the DNA from 78 normal volunteers. Southern hybridization experiments detected polymorphic HindIII, BamHI, and EcoRI sites. The presence of the polymorphic HindIII site results in a 7.0-kilobase (kb...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1980-09-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2007.12.011
更新日期:2008-03-01 00:00:00
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journal_title:American journal of human genetics
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更新日期:2009-10-01 00:00:00
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journal_title:American journal of human genetics
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更新日期:2015-08-06 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/515457
更新日期:1997-06-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.07.007
更新日期:2019-09-05 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301763
更新日期:1998-03-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.07.020
更新日期:2019-09-05 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302510
更新日期:1999-08-01 00:00:00
abstract::Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional a...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2017.09.018
更新日期:2017-11-02 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301632
更新日期:1997-12-01 00:00:00
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journal_title:American journal of human genetics
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doi:
更新日期:1996-10-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章,收录出版
doi:10.1016/j.ajhg.2011.05.009
更新日期:2011-06-10 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::A high incidence of 46,XX true hermaphroditism exists among southern African blacks. The gonadal distribution and clinical presentation of 38 patients are described. The aim of our study on 11 families with histologically proven XX true hermaphroditism was to determine whether a common genetic or environmental etiolog...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biolog...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals w...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.10.009
更新日期:2016-12-01 00:00:00
abstract::We have constructed a primary genetic map spanning most of human chromosome 13. A total of 14 polymorphic DNA sequences and one protein polymorphism provided, after construction of haplotypes, seven markers for the long arm of this chromosome. A panel of cell lines from 30 three-generation families with large sibship ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::The cellular mechanism for the expression of the fragile site at Xq28 is unknown. We tested the effect of 5-azacytidine and methionine on fragile X expression in lymphocytes and lymphoblastoid cells in an attempt to determine if DNA methylation was involved. We were unable to demonstrate a consistent dosage effect of ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00