A Mosaic PHEX Variant in Hypophosphatemic Rickets: Distinguishing Postzygotic Mutation from Sex Chromosome Aneuploidy
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Le résumé fourni par la source
Hereditary hypophosphatemic rickets, most commonly caused by X-linked dominant PHEX variants, leads to hypophosphatemia and bone mineralization defects. We identified a novel mosaic nonsense variant in the PHEX gene on the X chromosome by next-generation sequencing-c.1971C > A, p.(Tyr657X)--in a man with clinical features of hypophosphatemic rickets. As the variant was only found in 67% of DNA reads, we considered the possibility of sex chromosome aneuploidy (e.g. a 48,XXXY sex chromosome complement with an unaffected X chromosome i.e. variant on 2 of 3 X chromosomes producing a variant allele frequency of approx. 67%) or a postzygotic mutation resulting in the PHEX variant in some but not all cells. His mother was clinically unaffected, and he did not have features of Klinefelter's syndrome, favouring postzygotic mutation over sex chromosome aneuploidy. We excluded sex chromosome aneuploidy through karyotype studies showing a 46,XY status. As the event must therefore be a postzygotic variant to produce the reduced variant allele frequency, his parents are not at risk of having the variant. However, X chromosome postzygotic mutations in men may be inherited by female offspring (depending on the mosaic status of gonadal tissue). The patient's karyotype result was thus integral in the investigation of disease mechanism and in guiding family genetic counselling.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A Mosaic PHEX Variant in Hypophosphatemic Rickets: Distinguishing Postzygotic Mutation from Sex Chromosome Aneuploidy
- Date Crossref
- 18/06/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Royal Adelaide Hospital Endocrine and Metabolic Unit pays non établi dans la noticeÉtablissement de santé
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Queen Elizabeth Hospital Diabetes and Endocrine Service pays non établi dans la noticeÉtablissement de santé
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The University of Adelaide Adelaide Medical School pays non établi dans la noticeUniversité ou école supérieure
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South Australia Pathology pays non établi dans la noticeOrganisation à but non lucratif
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SA Pathology Department of Genetics & Molecular Pathology pays non établi dans la noticeEntreprise
Endocrine and Metabolic Unit — Royal Adelaide Hospital, Diabetes and Endocrine Service — Queen Elizabeth Hospital et Adelaide Medical School — The University of Adelaide, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.