X-linked recessive ichthyosis in 8 Tunisian patients: awareness of misdiagnosis due to the technical trap of the STS pseudogene.

Autor: Chouk H; Department of Cytogenetics, Molecular Genetic and Biology of Human Reproduction, Farhat Hached of Sousse, Sousse, Tunisia.; Higher Institute of Biotechnology of Monastir, Monastir, Tunisia., Saad S; Faculty of Medicine of Sousse, Sousse, Tunisia.; Department of Dermatology, Farhat Hached, Sousse, Tunisia., Dimassi S; Department of Cytogenetics, Molecular Genetic and Biology of Human Reproduction, Farhat Hached of Sousse, Sousse, Tunisia.; Faculty of Medicine of Sousse, Sousse, Tunisia., Fetoui NG; Faculty of Medicine of Sousse, Sousse, Tunisia.; Department of Dermatology, Farhat Hached, Sousse, Tunisia., Bennour A; Department of Cytogenetics, Molecular Genetic and Biology of Human Reproduction, Farhat Hached of Sousse, Sousse, Tunisia.; Faculty of Medicine of Sousse, Sousse, Tunisia., Gammoudi R; Faculty of Medicine of Sousse, Sousse, Tunisia.; Department of Dermatology, Farhat Hached, Sousse, Tunisia., Elmabrouk H; Department of Cytogenetics, Molecular Genetic and Biology of Human Reproduction, Farhat Hached of Sousse, Sousse, Tunisia.; Higher Institute of Biotechnology of Monastir, Monastir, Tunisia., Saad A; Department of Cytogenetics, Molecular Genetic and Biology of Human Reproduction, Farhat Hached of Sousse, Sousse, Tunisia.; Faculty of Medicine of Sousse, Sousse, Tunisia., Denguezli M; Faculty of Medicine of Sousse, Sousse, Tunisia.; Department of Dermatology, Farhat Hached, Sousse, Tunisia., H'mida D; Department of Cytogenetics, Molecular Genetic and Biology of Human Reproduction, Farhat Hached of Sousse, Sousse, Tunisia. dorrahmida@yahoo.fr.; Faculty of Medicine of Sousse, Sousse, Tunisia. dorrahmida@yahoo.fr.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2022 Jul 26; Vol. 15 (1), pp. 165. Date of Electronic Publication: 2022 Jul 26.
DOI: 10.1186/s12920-022-01319-4
Abstrakt: Introduction: X-linked recessive ichthyosis (XLI) is a genodermatosis, caused by a deficiency of the steroid sulphatase enzyme encoded by the STS gene (OMIM # 300,747). Adopted XLI molecular diagnosis approaches differ from one laboratory to another depending on available technical facilities. Our work aims to figure out a sound diagnostic strategy for XLI.
Patients and Methods: We collected 8 patients with XLI, all males, from 3 unrelated Tunisian families from central Tunisia. Genetic diagnosis was conducted through a large panel of genetic techniques including: Sanger Sequencing, haplotype analysis of STR markers, MLPA analysis, FISH and array CGH.
Results: Direct Sanger sequencing of the STS gene showed the same deletion of 13 base pairs within the exon 4 in all patients resulting in a premature stop codon. However, all patients' mothers were not carriers of this variant and no common haplotype flanking STS gene was shared between affected patients. Sequence alignment with reference human genome revealed an unprocessed pseudogene of the STS gene located on the Y chromosome, on which the 13 bp deletion was actually located. STS MLPA analysis identified a deletion of the entire STS gene on X chromosome for all affected patients. This deletion was confirmed by FISH and delineated by array CGH.
Conclusion: All our patients shared a deletion of the entire STS gene revealed by MLPA, confirmed by FISH and improved by array CGH. Geneticists must be aware of the presence of pseudogenes that can lead to XLI genetic misdiagnosis.
(© 2022. The Author(s).)
Databáze: MEDLINE
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