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      X‐linked ichthyosis: Molecular findings in four pedigrees with inconspicuous clinical manifestations

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          X‐linked ichthyosis (XLI) is the second most common type of ichthyosis, which is characterized by wide and symmetric distribution of adherent, dry, and polygonal scales on the skin. Steroid sulfatase ( STS) gene, which is located at chromosome Xp22.31, has been identified as the pathogenic gene of XLI.


          In this study, chromosome karyotype analysis, bacterial artificial chromosomes‐on‐Beads™ (BoBs) assay, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP‐array) were employed for the prenatal diagnoses in three pregnant women with high‐risk serological screening results and a pregnant woman with mental retardation.


          STS deletion was identified at chromosome Xp22.31 in all four fetuses. Postnatal follow‐up confirmed the diagnosis of ichthyosis in two male fetuses and revealed normal dermatological manifestations in other two female fetuses carrying ichthyosis.


          The results of the present study demonstrate that a combination of karyotypying, prenatal BoBs, FISH, and SNP‐array may avoid the missed detection of common microdeletions and ensure the accuracy of the detection results, which provides a feasible tool for the reliable etiological diagnosis and better genetic counseling of XLI.

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          Most cited references 19

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          Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis.

          X-linked ichthyosis is a relatively common syndromic form of ichthyosis most often due to deletions in the gene encoding the microsomal enzyme, steroid sulfatase, located on the short area of the X chromosome. Syndromic features are mild or unapparent unless contiguous genes are affected. In normal epidermis, cholesterol sulfate is generated by cholesterol sulfotransferase (SULT2B1b), but desulfated in the outer epidermis, together forming a 'cholesterol sulfate cycle' that potently regulates epidermal differentiation, barrier function and desquamation. In XLI, cholesterol sulfate levels my exceed 10% of total lipid mass (≈1% of total weight). Multiple cellular and biochemical processes contribute to the pathogenesis of the barrier abnormality and scaling phenotype in XLI. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
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            Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis.

            The pathological scaling in recessive x-linked ichthyosis is associated with accumulation of abnormal quantities of cholesterol sulfate in stratum corneum (J. Clin. Invest. 68:1404-1410, 1981). To determine whether or not cholesterol sulfate accumulates in recessive x-linked ichthyosis as a direct result of the missing enzyme, steroid sulfatase, we quantitated both steroid sulfatase and its substrate, we quantitated both steroid sulfatase and its substrate, cholesterol sulfate, in different epidermal strata, as well as within stratum corneum subcellular fractions obtained from normal human and neonatal mouse epidermis and from patients with recessive x-linked ichthyosis. In normal human and mouse epidermis, steroid sulfatase activity peaked in the stratum granulosum and stratum corneum, and negligible activity was detectable in lower epidermal layers. In contrast, in recessive x-linked ichthyosis epidermis, enzyme levels were virtually undetectable at all levels. In normal human stratum corneum, up to 10 times more steroid sulfatase activity was present in purified peripheral membrane preparations than in the whole tissue. Whereas in normal human epidermis cholesterol sulfate levels were lowest in the basal/spinous layer, and highest in the stratum granulosum, in recessive x-linked ichthyosis the levels were only slightly higher in the lower epidermis, but continued to climb in the stratum corneum. In both normal and in recessive x-linked ichthyosis stratum corneum, cholesterol sulfate appeared primarily within membrane domains, paralleling the pattern of steroid sulfatase localization. Finally, the role of excess cholesterol sulfate in the pathogenesis of recessive x-linked ichthyosis was directly tested by topical applications of this substance, which produced visible scaling in hairless mice in parallel to an increased cholesterol sulfate content of the stratum corneum. These results demonstrate an intimate relationship between steroid sulfatase and cholesterol sulfate in normal epidermis: both are concentrated in the outer epidermis (stratum corneum and stratum granulosum), and both are localized to membrane domains. Presumably, as a result of this distribution pattern, continued enzymatic degradation of substrate occurs in normal epidermis, thereby preventing excessive accumulation of cholesterol sulfate. In contrast, in recessive x-linked ichthyosis, degradation of cholesterol sulfate does not occur and cholesterol sulfate accumulates specifically in the stratum corneum, where it produces visible scale.
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              Nonsyndromic types of ichthyoses - an update.

              Ichthyoses are genetically determined Mendelian disorders of cornification (MEDOC) that are characterized by universal scaling. Today we distinguish between non-syndromic and syndromic forms. Ichthyosis vulgaris is the most frequent type (prevalence 1:100) and is caused by autosomal semi-dominant filaggrin mutations. It is associated with a higher risk for the development of atopic diseases, such as atopic eczema and allergic rhinitis. Recessive X-linked ichthyosis (RXLI) occurs almost exclusively in boys; in Germany it has a prevalence of around 1:4,000. It is caused by steroid sulfatase deficiency and is often associated with further clinical problems, such as cryptorchidism (∼20%) or social communication deficits, such as attention deficit hyperactivity syndrome (40%) or autism (25%). Autosomal recessive congenital ichthyosis (ARCI) is genetically very heterogeneous and 8 different genes have been identified so far. The most frequent cause of ARCI is a transglutaminase 1 deficiency (prevalence 1:200, 000). Mutations in keratin genes are the cause of the keratinopathic ichthyoses, such as epidermolytic ichthyosis. They manifest at birth and often feature episodes of blistering. Most of these types are inherited as autosomal dominant traits, but autosomal recessive forms have also been described on occasion.

                Author and article information

                J Clin Lab Anal
                J. Clin. Lab. Anal
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                16 January 2020
                May 2020
                : 34
                : 5 ( doiID: 10.1002/jcla.v34.5 )
                [ 1 ] Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect Fujian Maternity and Child Health Hospital Affiliated Hospital of Fujian Medical University Fuzhou China
                Author notes
                [* ] Correspondence

                Liangpu Xu, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou City, Fujian Province, 350001, China.

                Email: xiliangpu@ 123456fjmu.edu.cn

                © 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Figures: 3, Tables: 2, Pages: 9, Words: 4796
                Funded by: the Key Clinical Specialty Discipline Construction Program of Fujian
                Award ID: 20121589
                Funded by: the Key Special Projects of Fujian Provincial Department of Science and Technology
                Award ID: 2013YZ0002‐
                Funded by: the Fujian Provincial Natural Science Foundation
                Award ID: 2017J01238
                Research Article
                Research Articles
                Custom metadata
                May 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.2 mode:remove_FC converted:25.05.2020


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